BioPAX pathway converted from "Transcriptional Regulation by TP53" in the Reactome database.Transcriptional Regulation by TP53This event has been computationally inferred from an event that has been demonstrated in another species.<p>The inference is based on the homology mapping from PANTHER. Briefly, reactions for which all involved PhysicalEntities (in input, output and catalyst) have a mapped orthologue/paralogue (for complexes at least 75% of components must have a mapping) are inferred to the other species. High level events are also inferred for these events to allow for easier navigation.<p><a href='/electronic_inference_compara.html' target = 'NEW'>More details and caveats of the event inference in Reactome.</a> For details on PANTHER see also: <a href='http://www.pantherdb.org/about.jsp' target='NEW'>http://www.pantherdb.org/about.jsp</a>TP53 Regulates Metabolic GenesThis event has been computationally inferred from an event that has been demonstrated in another species.<p>The inference is based on the homology mapping from PANTHER. Briefly, reactions for which all involved PhysicalEntities (in input, output and catalyst) have a mapped orthologue/paralogue (for complexes at least 75% of components must have a mapping) are inferred to the other species. High level events are also inferred for these events to allow for easier navigation.<p><a href='/electronic_inference_compara.html' target = 'NEW'>More details and caveats of the event inference in Reactome.</a> For details on PANTHER see also: <a href='http://www.pantherdb.org/about.jsp' target='NEW'>http://www.pantherdb.org/about.jsp</a>LEFT-TO-RIGHT3.1.3.46TIGAR converts D-fructose-2,6-bisphosphate to D-fructose 6-phosphateThis event has been computationally inferred from an event that has been demonstrated in another species.<p>The inference is based on the homology mapping from PANTHER. Briefly, reactions for which all involved PhysicalEntities (in input, output and catalyst) have a mapped orthologue/paralogue (for complexes at least 75% of components must have a mapping) are inferred to the other species. High level events are also inferred for these events to allow for easier navigation.<p><a href='/electronic_inference_compara.html' target = 'NEW'>More details and caveats of the event inference in Reactome.</a> For details on PANTHER see also: <a href='http://www.pantherdb.org/about.jsp' target='NEW'>http://www.pantherdb.org/about.jsp</a>D-Fructose 2,6-bisphosphatebeta-D-fructofuranose 2,6-bisphosphateReactome DB_ID: 30533cytosolGENE ONTOLOGYGO:0005829beta-D-fructofuranose 2,6-bisphosphate [ChEBI:28602]beta-D-fructofuranose 2,6-bisphosphateChEBICHEBI:28602Reactome Database ID Release 7530533Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=30533ReactomeR-ALL-305333Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-ALL-30533.3Reactomehttp://www.reactome.orgCOMPOUNDC00665additional informationMIMI:0361H2OwaterReactome DB_ID: 29356water [ChEBI:15377]waterChEBICHEBI:15377Reactome Database ID Release 7529356Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=29356ReactomeR-ALL-293565Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-ALL-29356.5COMPOUNDC00001Fru(6)PD-Fructose 6-phosphateketo-D-fructose 6-phosphateD-Fructose 6-phosphoric acidNeuberg esterD-fructose 6-phosphate(2-)Reactome DB_ID: 29512beta-D-fructofuranose 6-phosphate(2-) [ChEBI:57634]beta-D-fructofuranose 6-phosphate(2-)beta-D-fructofuranose 6-phosphate dianion6-O-phosphonato-beta-D-fructofuranoseChEBICHEBI:57634Reactome Database ID Release 7529512Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=29512ReactomeR-ALL-295124Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-ALL-29512.4COMPOUNDC00085PiOrthophosphatehydrogenphosphatePhosphateInorganic PhosphateReactome DB_ID: 29372hydrogenphosphate [ChEBI:43474]hydrogenphosphatehydrogen phosphatephosphate[PO3(OH)](2-)INORGANIC PHOSPHATE GROUPHYDROGENPHOSPHATE IONHPO4(2-)[P(OH)O3](2-)ChEBICHEBI:43474Reactome Database ID Release 7529372Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=29372ReactomeR-ALL-293724Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-ALL-29372.4COMPOUNDC00009ACTIVATIONTIGARR4GIZ6Reactome DB_ID: 10464609UniProt:R4GIZ6Gallus gallusNCBI Taxonomy9031UniProtR4GIZ61EQUAL270EQUALReactome Database ID Release 7510464609Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10464609ReactomeR-GGA-56288291Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-GGA-5628829.1GENE ONTOLOGYGO:0004331gene ontology term for cellular functionMIMI:0355Same Catalyst ActivityReactome Database ID Release 7510464610Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10464610Reactome Database ID Release 7510464612Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10464612ReactomeR-GGA-56289051Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-GGA-5628905.1TIGAR shares similarity with PGMs (phosphoglycerate mutases), especially PFK2 (6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase). TIGAR possesses only the bisphosphatase domain and converts D-fructose 2,6-bisphosphate into D-fructose 6-phosphate (Bensaad et al. 2006). Reduction of fructose 2,6-bisphosphate levels correlates with decrease in glycolytic rates, which makes cells more sensitive to apoptotic stimuli (Vander Heiden et al. 2001). Alternatively, fructose 6-phosphate can be isomerized to glucose 6-phosphate, which is diverted to the pentose phosphate pathway, which can have an anti-apoptotic effect (Boada et al. 2000, Perez et al. 2000). In the pentose phosphate pathway, oxidized glutathione is reduced, and this reduced glutathione can then be used by glutathione peroxidase to remove hydrogen peroxide, thereby protecting cells from the oxidative stress (Kletzien et al. 1994, Fico et al. 2004, Tian et al. 1999). Indeed, expression of TIGAR increases reduced glutathione to oxidized glutathione ratio and lowers ROS (reactive oxygen species) levels in cells (Bensaad et al. 2006, Lee et al. 2014). 15044966Pubmed2004Glucose-6-phosphate dehydrogenase plays a crucial role in protection from redox-stress-induced apoptosisFico, APaglialunga, FCigliano, LAbrescia, PVerde, PMartini, GIaccarino, IFilosa, SCell Death Differ. 11:823-318119488Pubmed1994Glucose-6-phosphate dehydrogenase: a "housekeeping" enzyme subject to tissue-specific regulation by hormones, nutrients, and oxidant stressKletzien, R FHarris, P KFoellmi, L AFASEB J. 8:174-8110329961Pubmed1999Importance of glucose-6-phosphate dehydrogenase activity in cell deathTian, W NBraunstein, L DApse, KPang, JRose, MTian, XStanton, R CAm. J. Physiol. 276:C1121-3111486029Pubmed2001Growth factors can influence cell growth and survival through effects on glucose metabolismVander Heiden, M GPlas, D RRathmell, J CFox, C JHarris, M HThompson, C BMol. Cell. Biol. 21:5899-91224383451Pubmed2014TIGAR, TIGAR, burning brightLee, PearlVousden, Karen HCheung, Eric CCancer Metab 2:111029283Pubmed2000Overexpression of fructose 2,6-bisphosphatase decreases glycolysis and delays cell cycle progressionPerez, J XRoig, TManzano, ADalmau, MBoada, JVentura, FRosa, J LBermudez, JBartrons, RAm. J. Physiol., Cell Physiol. 279:C1359-6516839880Pubmed2006TIGAR, a p53-inducible regulator of glycolysis and apoptosisBensaad, KarimTsuruta, AtsushiSelak, Mary AVidal, M Nieves CalvoNakano, KatsunoriBartrons, RamonGottlieb, EyalVousden, Karen HCell 126:107-2011034341Pubmed2000Cells overexpressing fructose-2,6-bisphosphatase showed enhanced pentose phosphate pathway flux and resistance to oxidative stressBoada, JRoig, TPerez, XGámez, ABartrons, RCascante, MBermúdez, JFEBS Lett. 480:261-4inferred from electronic annotationEVIDENCE CODEECO:0000203LEFT-TO-RIGHT5.3.1.9D-fructose 6-phosphate <=> alpha-D-Glucose 6-phosphateThis event has been computationally inferred from an event that has been demonstrated in another species.<p>The inference is based on the homology mapping from PANTHER. Briefly, reactions for which all involved PhysicalEntities (in input, output and catalyst) have a mapped orthologue/paralogue (for complexes at least 75% of components must have a mapping) are inferred to the other species. High level events are also inferred for these events to allow for easier navigation.<p><a href='/electronic_inference_compara.html' target = 'NEW'>More details and caveats of the event inference in Reactome.</a> For details on PANTHER see also: <a href='http://www.pantherdb.org/about.jsp' target='NEW'>http://www.pantherdb.org/about.jsp</a>G6Palpha-D-glucose 6-phosphatealpha-D-glucose 6-phosphate(2-)Reactome DB_ID: 30537alpha-D-glucose 6-phosphate(2-) [ChEBI:58225]alpha-D-glucose 6-phosphate(2-)alpha-D-glucopyranose 6-phosphatealpha-D-glucose 6-phosphate dianionalpha-D-glucose 6-phosphate6-O-phosphonato-alpha-D-glucopyranoseChEBICHEBI:58225Reactome Database ID Release 7530537Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=30537ReactomeR-ALL-305374Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-ALL-30537.4COMPOUNDC00668ACTIVATIONGPI dimerReactome DB_ID: 10413997GPIGPIA0A1L1RQ91Reactome DB_ID: 10413995UniProt:A0A1L1RQ91GPIUniProtA0A1L1RQ912EQUAL558EQUALReactome Database ID Release 7510413995Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10413995ReactomeR-GGA-704681Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-GGA-70468.12Reactome Database ID Release 7510413997Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10413997ReactomeR-GGA-704691Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-GGA-70469.1GENE ONTOLOGYGO:0004347Reactome Database ID Release 7510413998Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10413998Reactome Database ID Release 7510414002Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10414002ReactomeR-GGA-704751Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-GGA-70475.1The reversible isomerization of fructose-6-phosphate to form glucose-6-phosphate is catalyzed by cytosolic phosphoglucose isomerase (Noltman 1972; Xu and Beutler 1994; Tsuboi et al. 1958).0121227022ISBN1972Aldose-ketose isomerasesNoltmann, EAThe Enzymes, 3rd ed (Book): 271-3547989588Pubmed1994The characterization of gene mutations for human glucose phosphate isomerase deficiency associated with chronic hemolytic anemiaXu, WBeutler, ErnestJ Clin Invest 94:2326-913538944Pubmed1958Enzymes of the human erythrocyte. IV. Phosphoglucose isomerase, purification and properties.Tsuboi, KKEstrada, JHudson, PBJ Biol Chem 231:19-29LEFT-TO-RIGHT1.8.1.7glutathione (oxidized) + NADPH + H+ => 2 glutathione (reduced) + NADP+This event has been computationally inferred from an event that has been demonstrated in another species.<p>The inference is based on the homology mapping from PANTHER. Briefly, reactions for which all involved PhysicalEntities (in input, output and catalyst) have a mapped orthologue/paralogue (for complexes at least 75% of components must have a mapping) are inferred to the other species. High level events are also inferred for these events to allow for easier navigation.<p><a href='/electronic_inference_compara.html' target = 'NEW'>More details and caveats of the event inference in Reactome.</a> For details on PANTHER see also: <a href='http://www.pantherdb.org/about.jsp' target='NEW'>http://www.pantherdb.org/about.jsp</a>TPNHNADPHReactome DB_ID: 29364NADPH [ChEBI:16474]NADPHTPNHChEBICHEBI:16474Reactome Database ID Release 7529364Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=29364ReactomeR-ALL-293642Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-ALL-29364.2COMPOUNDC00005GSSGoxidized glutathioneglutathione disulfideReactome DB_ID: 111745glutathione disulfide [ChEBI:17858]glutathione disulfideChEBICHEBI:17858Reactome Database ID Release 75111745Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=111745ReactomeR-ALL-1117453Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-ALL-111745.3COMPOUNDC00127H+protonhydronReactome DB_ID: 70106hydron [ChEBI:15378]hydronChEBICHEBI:15378Reactome Database ID Release 7570106Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=70106ReactomeR-ALL-701064Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-ALL-70106.4COMPOUNDC00080GSHReduced glutathioneglutathione5-L-Glutamyl-L-cysteinylglycineN-(N-gamma-L-Glutamyl-L-cysteinyl)glycinegamma-L-Glutamyl-L-cysteinyl-glycineReactome DB_ID: 29450glutathione [ChEBI:16856]glutathioneChEBICHEBI:16856Reactome Database ID Release 7529450Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=29450ReactomeR-ALL-294503Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-ALL-29450.3COMPOUNDC000512TPNNADP+NADPNADP(+)Nicotinamide adenine dinucleotide phosphatebeta-Nicotinamide adenine dinucleotide phosphateTriphosphopyridine nucleotideReactome DB_ID: 29366NADP(+) [ChEBI:18009]NADP(+)ChEBICHEBI:18009Reactome Database ID Release 7529366Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=29366ReactomeR-ALL-293663Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-ALL-29366.3COMPOUNDC00006ACTIVATIONGSR-2:FAD dimerReactome DB_ID: 10414835FADFlavin adenine dinucleotideReactome DB_ID: 29386FAD [ChEBI:16238]FADFlavin adenine dinucleotideChEBICHEBI:16238Reactome Database ID Release 7529386Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=29386ReactomeR-ALL-293862Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-ALL-29386.2COMPOUNDC000162GSR-2A0A1D5P338Reactome DB_ID: 10414833UniProt:A0A1D5P338UniProtA0A1D5P33844EQUAL522EQUALReactome Database ID Release 7510414833Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10414833ReactomeR-GGA-716791Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-GGA-71679.12Reactome Database ID Release 7510414835Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10414835ReactomeR-GGA-716801Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-GGA-71680.1GENE ONTOLOGYGO:0004362Reactome Database ID Release 7510414836Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10414836Reactome Database ID Release 7510414838Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10414838ReactomeR-GGA-716821Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-GGA-71682.1Cytosolic glutathione reductase catalyzes the reaction of glutathione (oxidized) and NADPH + H+ to form two molecules of glutathione (reduced) and NADP+ (Scott et al. 1963, Loos et al. 1976). Deficiency of glutathione reductase can cause hemolytic anemia.14086726Pubmed1963PURIFICATION AND PROPERTIES OF GLUTATHIONE REDUCTASE OF HUMAN ERYTHROCYTESSCOTT, E MDUNCAN, I WEKSTRAND, VJ. Biol. Chem. 238:3928-33947404Pubmed1976Familial deficiency of glutathione reductase in human blood cellsLoos, HRoos, DWeening, RHouwerzijl, JBlood 48:53-62LEFT-TO-RIGHT1.11.1PRDX1,2,5 catalyze TXN reduced + H2O2 => TXN oxidized + 2H2OThis event has been computationally inferred from an event that has been demonstrated in another species.<p>The inference is based on the homology mapping from PANTHER. Briefly, reactions for which all involved PhysicalEntities (in input, output and catalyst) have a mapped orthologue/paralogue (for complexes at least 75% of components must have a mapping) are inferred to the other species. High level events are also inferred for these events to allow for easier navigation.<p><a href='/electronic_inference_compara.html' target = 'NEW'>More details and caveats of the event inference in Reactome.</a> For details on PANTHER see also: <a href='http://www.pantherdb.org/about.jsp' target='NEW'>http://www.pantherdb.org/about.jsp</a>H2O2hydrogen peroxideReactome DB_ID: 29408hydrogen peroxide [ChEBI:16240]hydrogen peroxideChEBICHEBI:16240Reactome Database ID Release 7529408Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=29408ReactomeR-ALL-294083Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-ALL-29408.3COMPOUNDC00027TXNTXNP08629Reactome DB_ID: 10416220UniProt:P08629TXNUniProtP086292EQUAL105EQUALReactome Database ID Release 7510416220Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10416220ReactomeR-GGA-660001Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-GGA-66000.1TXN2xHC-TXNP08629Reactome DB_ID: 1041621832EQUALL-cystine (cross-link)MODMOD:000342EQUAL105EQUALReactome Database ID Release 7510416218Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10416218ReactomeR-GGA-736681Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-GGA-73668.12ACTIVATIONPRDX1 dimerReactome DB_ID: 10458719PRDX1P0CB50Reactome DB_ID: 10458717UniProt:P0CB50UniProtP0CB502EQUAL199EQUALReactome Database ID Release 7510458717Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10458717ReactomeR-GGA-33412701Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-GGA-3341270.12Reactome Database ID Release 7510458719Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10458719ReactomeR-GGA-33413191Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-GGA-3341319.1GENE ONTOLOGYGO:0008379Reactome Database ID Release 7510458720Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10458720Reactome Database ID Release 7510458722Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10458722ReactomeR-GGA-33413431Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-GGA-3341343.1Peroxiredoxin 1 (PRDX1), PRDX2, and PRDX5 in the cytosol reduce hydrogen peroxide (H2O2) with thioredoxin yielding oxidized thioredoxin and water (Yamashita et al. 1999, Lee et al. 2007, Nagy et al. 2011).10514471Pubmed1999Characterization of human and murine PMP20 peroxisomal proteins that exhibit antioxidant activity in vitroYamashita, HAvraham, SJiang, SLondon, RVan Veldhoven, Paul PSubramani, SRogers, R AAvraham, HJ. Biol. Chem. 274:29897-90421385867Pubmed2011Model for the exceptional reactivity of peroxiredoxins 2 and 3 with hydrogen peroxide: a kinetic and computational studyNagy, PéterKarton, AmirBetz, AndreaPeskin, Alexander VPace, PaulO'Reilly, Robert JHampton, Mark BRadom, LeoWinterbourn, Christine CJ. Biol. Chem. 286:18048-5517519234Pubmed2007Human peroxiredoxin 1 and 2 are not duplicate proteins: the unique presence of CYS83 in Prx1 underscores the structural and functional differences between Prx1 and Prx2Lee, WeonsupChoi, Kyoung-SooRiddell, JonahIp, ClementGhosh, DebashisPark, Jong-HoonPark, Young-MeeJ. Biol. Chem. 282:22011-22LEFT-TO-RIGHT1.8.1.9regeneration of active (reduced) Thioredoxinthioredoxin, oxidized + NADPH + H+ => thioredoxin, reduced + NADP+This event has been computationally inferred from an event that has been demonstrated in another species.<p>The inference is based on the homology mapping from PANTHER. Briefly, reactions for which all involved PhysicalEntities (in input, output and catalyst) have a mapped orthologue/paralogue (for complexes at least 75% of components must have a mapping) are inferred to the other species. High level events are also inferred for these events to allow for easier navigation.<p><a href='/electronic_inference_compara.html' target = 'NEW'>More details and caveats of the event inference in Reactome.</a> For details on PANTHER see also: <a href='http://www.pantherdb.org/about.jsp' target='NEW'>http://www.pantherdb.org/about.jsp</a>ACTIVATIONTNXRD1:FAD dimerReactome DB_ID: 10416226TXNRD1A0A1D5PXN5Reactome DB_ID: 10416224UniProt:A0A1D5PXN5UniProtA0A1D5PXN51EQUAL649EQUALReactome Database ID Release 7510416224Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10416224ReactomeR-GGA-735311Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-GGA-73531.122Reactome Database ID Release 7510416226Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10416226ReactomeR-GGA-735321Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-GGA-73532.1GENE ONTOLOGYGO:0004791Reactome Database ID Release 7510416227Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10416227Reactome Database ID Release 7510416229Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10416229ReactomeR-GGA-736461Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-GGA-73646.1Cytosolic thioredoxin reductase catalyzes the reaction of thioredoxin, oxidized and NADPH + H+ to form thioredoxin, reduced and NADP+ (Urig et al. 2006).16750198Pubmed2006Truncated mutants of human thioredoxin reductase 1 do not exhibit glutathione reductase activityUrig, SLieske, JFritz-Wolf, KIrmler, ABecker, KFEBS Lett 580:3595-600LEFT-TO-RIGHT1.11.1.7PRDX1 overoxidizesThis event has been computationally inferred from an event that has been demonstrated in another species.<p>The inference is based on the homology mapping from PANTHER. Briefly, reactions for which all involved PhysicalEntities (in input, output and catalyst) have a mapped orthologue/paralogue (for complexes at least 75% of components must have a mapping) are inferred to the other species. High level events are also inferred for these events to allow for easier navigation.<p><a href='/electronic_inference_compara.html' target = 'NEW'>More details and caveats of the event inference in Reactome.</a> For details on PANTHER see also: <a href='http://www.pantherdb.org/about.jsp' target='NEW'>http://www.pantherdb.org/about.jsp</a>2HOOS-C52-PRDX1 dimerReactome DB_ID: 104646171P0CB50HOOS-C52-PRDX1Reactome DB_ID: 1046461552EQUALL-cysteine sulfinic acidMODMOD:002672EQUAL199EQUALReactome Database ID Release 7510464615Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10464615ReactomeR-GGA-56291981Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-GGA-5629198.11Reactome Database ID Release 7510464617Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10464617ReactomeR-GGA-56318821Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-GGA-5631882.1ACTIVATIONactiveUnit: #Protein6GENE ONTOLOGYGO:0004601Reactome Database ID Release 7510464618Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10464618Reactome Database ID Release 7510464620Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10464620ReactomeR-GGA-56318851Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-GGA-5631885.1The activity of eukaryotic PRDX1 gradually decreases with time, which is due to the overoxidation of the catalytic cysteine C52. Normally, oxidized cysteine C52-SOH is generated as a catalytic intermediate, which is subsequently reduced by thioredoxin. Occasionally, further oxidation happens, generating C52-SOOH , where the catalytic cysteine is converted to cysteine-sulfinic acid. This over-oxidation cannot be reversed by thioredoxin (Yang et al. 2002, Budanov et al. 2004). Bacterial peroxiredoxin AhpC does not undergo over-oxidation due to structural difference (Wood et al. 2003).12161445Pubmed2002Inactivation of human peroxiredoxin I during catalysis as the result of the oxidation of the catalytic site cysteine to cysteine-sulfinic acidYang, Kap-SeokKang, Sang WonWoo, Hyun AeHwang, Sung ChulChae, Ho ZoonKim, KanghwaRhee, Sue GooJ. Biol. Chem. 277:38029-3612714747Pubmed2003Peroxiredoxin evolution and the regulation of hydrogen peroxide signalingWood, Zachary APoole, Leslie BKarplus, P AndrewScience 300:650-315105503Pubmed2004Regeneration of peroxiredoxins by p53-regulated sestrins, homologs of bacterial AhpDBudanov, Andrei VSablina, Anna AFeinstein, ElenaKoonin, Eugene VChumakov, Peter MScience 304:596-600LEFT-TO-RIGHTSestrins bind overoxidized PRDX1SESN1,2,3 bind overoxidized PRDX1This event has been computationally inferred from an event that has been demonstrated in another species.<p>The inference is based on the homology mapping from PANTHER. Briefly, reactions for which all involved PhysicalEntities (in input, output and catalyst) have a mapped orthologue/paralogue (for complexes at least 75% of components must have a mapping) are inferred to the other species. High level events are also inferred for these events to allow for easier navigation.<p><a href='/electronic_inference_compara.html' target = 'NEW'>More details and caveats of the event inference in Reactome.</a> For details on PANTHER see also: <a href='http://www.pantherdb.org/about.jsp' target='NEW'>http://www.pantherdb.org/about.jsp</a>Converted from EntitySet in ReactomeSESN1,2,3Reactome DB_ID: 10464638SESN2LOC100858796A0A1D5PKB0Reactome DB_ID: 10464624UniProt:A0A1D5PKB0LOC100858796UniProtA0A1D5PKB01EQUAL480EQUALReactome Database ID Release 7510464624Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10464624ReactomeR-GGA-56291431Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-GGA-5629143.1Converted from EntitySet in ReactomeSESN1-1,SESN1-3Sestrin 1 isoforms T2 and T3PA26 isoforms T2 and T3Reactome DB_ID: 10464632SESN1-1A0A1D5P711Reactome DB_ID: 10464628UniProt:A0A1D5P711UniProtA0A1D5P7111EQUAL492EQUALReactome Database ID Release 7510464628Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10464628ReactomeR-GGA-56291481Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-GGA-5629148.1SESN1-3A0A1D5P711Reactome DB_ID: 104646301EQUAL426EQUALReactome Database ID Release 7510464630Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10464630ReactomeR-GGA-56291791Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-GGA-5629179.1Reactome Database ID Release 7510464632Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10464632ReactomeR-GGA-56291861Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-GGA-5629186.1SESN3SESN3A0A3Q2UJ63Reactome DB_ID: 10464636UniProt:A0A3Q2UJ63SESN3UniProtA0A3Q2UJ631EQUAL492EQUALReactome Database ID Release 7510464636Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10464636ReactomeR-GGA-56291441Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-GGA-5629144.1Reactome Database ID Release 7510464638Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10464638ReactomeR-GGA-56291911Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-GGA-5629191.1SESN1,2,3:HOOS-C52-PRDX1 dimerReactome DB_ID: 1046464011Reactome Database ID Release 7510464640Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10464640ReactomeR-GGA-56319021Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-GGA-5631902.1Reactome Database ID Release 7510464642Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10464642ReactomeR-GGA-56319031Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-GGA-5631903.1Sestrins (SESN1, SESN2 and likely SESN3) bind overoxidized PRDX1, in which the catalytic cysteine C52 has been converted to cysteine-sulfinic acid. Among all peroxiredoxins, PRDX1 is the most abundant member of the PRDX family. The major function is to protect cells against reactive oxygen species (ROS), thus impacting on cell proliferation and survival (Gong et al. 2015). While several reports state that sestrins reduce overoxidized PRDX1 to the catalytically active homodimer (Budanov et al. 2004, Papadia et al. 2008, Essler et al. 2009), there are conflicting reports claiming that sestrins do not possess cysteine sulfinyl reductase activity (Woo et al. 2009). 18344994Pubmed2008Synaptic NMDA receptor activity boosts intrinsic antioxidant defensesPapadia, SofiaSoriano, Francesc XLéveillé, FrédéricMartel, Marc-AndreDakin, Kelly AHansen, Henrik HKaindl, AngelaSifringer, MarcoFowler, JillStefovska, VanyaMcKenzie, GrahameCraigon, MarieCorriveau, RoderickGhazal, PeterHorsburgh, KarenYankner, Bruce AWyllie, David J AIkonomidou, ChrysanthyHardingham, Giles ENat. Neurosci. 11:476-8719822145Pubmed2009Role of sestrin2 in peroxide signaling in macrophagesEssler, SilkeDehne, NathalieBrüne, BernhardFEBS Lett. 583:3531-519113821Pubmed2009Sestrin 2 is not a reductase for cysteine sulfinic acid of peroxiredoxinsWoo, Hyun AeBae, Soo HanPark, SunjooRhee, Sue GooAntioxid. Redox Signal. 11:739-4525579166Pubmed2015Peroxiredoxin 1 promotes tumorigenesis through regulating the activity of mTOR/p70S6K pathway in esophageal squamous cell carcinomaGong, FanghuaHou, GuiqinLiu, HongtaoZhang, MingzhiMed. Oncol. 32:455LEFT-TO-RIGHT3.6.5.43.6.5.33.6.5.23.6.5.1RHEB in mTORC1:RHEB:GTP hydrolyses GTPThis event has been computationally inferred from an event that has been demonstrated in another species.<p>The inference is based on the homology mapping from PANTHER. Briefly, reactions for which all involved PhysicalEntities (in input, output and catalyst) have a mapped orthologue/paralogue (for complexes at least 75% of components must have a mapping) are inferred to the other species. High level events are also inferred for these events to allow for easier navigation.<p><a href='/electronic_inference_compara.html' target = 'NEW'>More details and caveats of the event inference in Reactome.</a> For details on PANTHER see also: <a href='http://www.pantherdb.org/about.jsp' target='NEW'>http://www.pantherdb.org/about.jsp</a>Active mTORC1 complexReactome DB_ID: 10422036lysosomal membraneGENE ONTOLOGYGO:0005765RHEB:GTPReactome DB_ID: 10421960GTPGuanosine 5'-triphosphateReactome DB_ID: 29438GTP [ChEBI:15996]GTPGuanosine 5'-triphosphateChEBICHEBI:15996Reactome Database ID Release 7529438Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=29438ReactomeR-ALL-294383Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-ALL-29438.3COMPOUNDC000441RHEBA0A3Q3AUL4Reactome DB_ID: 10421956UniProt:A0A3Q3AUL4UniProtA0A3Q3AUL41EQUAL181EQUALReactome Database ID Release 7510421956Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10421956ReactomeR-GGA-1651901Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-GGA-165190.11Reactome Database ID Release 7510421960Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10421960ReactomeR-GGA-1651891Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-GGA-165189.11mTORC1:Ragulator:RagA,B:GTP:RagC,D:GDP:SLC38A9Reactome DB_ID: 10422034Ragulator:RagA,B:GTP:RagC,D:GDP:SLC38A9Reactome DB_ID: 10422032E1C2K4SLC38A9SLC38A9Reactome DB_ID: 10421980UniProt:E1C2K4SLC38A9UniProtE1C2K41EQUAL561EQUALReactome Database ID Release 7510421980Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10421980ReactomeR-GGA-52159381Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-GGA-5215938.11Ragulator:RagA,B:GTP:RagC,D:GDPReactome DB_ID: 10422030RagA,B:GTP:RagC,D:GDPReactome DB_ID: 10422028Converted from EntitySet in ReactomeRRAGC,RRAGD:GDPReactome DB_ID: 10422026RRAGC:GDPReactome DB_ID: 10422018RRAGCRRAGCA0A1D5PLJ0Reactome DB_ID: 10422016UniProt:A0A1D5PLJ0RRAGCUniProtA0A1D5PLJ02EQUAL399EQUALReactome Database ID Release 7510422016Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10422016ReactomeR-GGA-56539491Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-GGA-5653949.11GDPGuanosine 5'-diphosphateGuanosine diphosphateReactome DB_ID: 29420GDP [ChEBI:17552]GDPGuanosine 5'-diphosphateGuanosine diphosphateChEBICHEBI:17552Reactome Database ID Release 7529420Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=29420ReactomeR-ALL-294202Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-ALL-29420.2COMPOUNDC000351Reactome Database ID Release 7510422018Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10422018ReactomeR-GGA-56539731Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-GGA-5653973.1RRAGD:GDPReactome DB_ID: 10422024RRAGDR4GK54Reactome DB_ID: 10422022UniProt:R4GK54UniProtR4GK541EQUAL400EQUALReactome Database ID Release 7510422022Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10422022ReactomeR-GGA-56539531Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-GGA-5653953.111Reactome Database ID Release 7510422024Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10422024ReactomeR-GGA-56539701Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-GGA-5653970.1Reactome Database ID Release 7510422026Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10422026ReactomeR-GGA-56539641Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-GGA-5653964.11Converted from EntitySet in ReactomeRRAGA, RRAGB:GTPReactome DB_ID: 10422012RRAGA:GTPReactome DB_ID: 10422006RRAGARRAGAA0A1D5PFS2Reactome DB_ID: 10422004UniProt:A0A1D5PFS2RRAGAUniProtA0A1D5PFS21EQUAL313EQUALReactome Database ID Release 7510422004Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10422004ReactomeR-GGA-56535771Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-GGA-5653577.111Reactome Database ID Release 7510422006Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10422006ReactomeR-GGA-56539781Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-GGA-5653978.1RRAGB:GTPReactome DB_ID: 10422010RRAGARRAGBA0A1D5PFS2Reactome DB_ID: 104220081EQUAL374EQUALReactome Database ID Release 7510422008Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10422008ReactomeR-GGA-56535791Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-GGA-5653579.111Reactome Database ID Release 7510422010Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10422010ReactomeR-GGA-56539761Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-GGA-5653976.1Reactome Database ID Release 7510422012Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10422012ReactomeR-GGA-56539461Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-GGA-5653946.11Reactome Database ID Release 7510422028Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10422028ReactomeR-GGA-56539451Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-GGA-5653945.11RagulatorReactome DB_ID: 10422000LAMTOR3A0A452J856Reactome DB_ID: 10421992UniProt:A0A452J856UniProtA0A452J8561EQUAL124EQUALReactome Database ID Release 7510421992Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10421992ReactomeR-GGA-56535811Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-GGA-5653581.11LAMTOR1A0A3Q2TWF2Reactome DB_ID: 10421984UniProt:A0A3Q2TWF2UniProtA0A3Q2TWF22EQUAL161EQUALReactome Database ID Release 7510421984Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10421984ReactomeR-GGA-56535821Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-GGA-5653582.11Ghost homologue of LAMTOR4Reactome DB_ID: 10421994Reactome Database ID Release 7510421994Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10421994ReactomeR-GGA-56554321Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-GGA-5655432.11F1NRX4LAMTOR5Reactome DB_ID: 10421998UniProt:F1NRX4UniProtF1NRX41EQUAL91EQUALReactome Database ID Release 7510421998Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10421998ReactomeR-GGA-56554411Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-GGA-5655441.11LAMTOR2A0A1D5PYY2Reactome DB_ID: 10421988UniProt:A0A1D5PYY2UniProtA0A1D5PYY21EQUAL125EQUALReactome Database ID Release 7510421988Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10421988ReactomeR-GGA-56535831Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-GGA-5653583.11Reactome Database ID Release 7510422000Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10422000ReactomeR-GGA-56539211Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-GGA-5653921.11Reactome Database ID Release 7510422030Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10422030ReactomeR-GGA-56539791Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-GGA-5653979.11Reactome Database ID Release 7510422032Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10422032ReactomeR-GGA-89527251Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-GGA-8952725.11mTORC1Reactome DB_ID: 10421976MTORF1NUX4Reactome DB_ID: 10421970UniProt:F1NUX4UniProtF1NUX41EQUAL2549EQUALReactome Database ID Release 7510421970Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10421970ReactomeR-GGA-1656621Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-GGA-165662.11MLST8MLST8F1NAZ4Reactome DB_ID: 10421966UniProt:F1NAZ4MLST8UniProtF1NAZ41EQUAL326EQUALReactome Database ID Release 7510421966Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10421966ReactomeR-GGA-1656761Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-GGA-165676.11RPTORRPTORA0A3Q2UCT4Reactome DB_ID: 10421974UniProt:A0A3Q2UCT4RPTORUniProtA0A3Q2UCT41EQUAL1335EQUALReactome Database ID Release 7510421974Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10421974ReactomeR-GGA-30067271Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-GGA-3006727.11Reactome Database ID Release 7510421976Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10421976ReactomeR-GGA-3774001Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-GGA-377400.11Reactome Database ID Release 7510422034Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10422034ReactomeR-GGA-56539721Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-GGA-5653972.11Reactome Database ID Release 7510422036Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10422036ReactomeR-GGA-1656781Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-GGA-165678.1mTORC1:Ragulator:Rag:GNP:RHEB:GDPReactome DB_ID: 104331481RHEB:GDPReactome DB_ID: 1042195811Reactome Database ID Release 7510421958Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10421958ReactomeR-GGA-1651911Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-GGA-165191.11Reactome Database ID Release 7510433148Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10433148ReactomeR-GGA-56934471Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-GGA-5693447.1ACTIVATIONactiveUnit: #Protein14GENE ONTOLOGYGO:0003924Reactome Database ID Release 7510433149Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10433149Reactome Database ID Release 7510433151Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10433151ReactomeR-GGA-3809791Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-GGA-380979.1TSC2 (in the TSC complex) functions as a GTPase-activating protein and stimulates the intrinsic GTPase activity of the small G-protein Rheb. This results in the conversion of Rheb:GTP to Rheb:GDP. GDP-bound Rheb is unable to activate mTOR (Inoki et al. 2003, Tee et al. 2003). It is not demonstrated that RHEB hydrolyzes GTP when present in the mTORC1 complex; given the low affinity of RHEB for mTOR, it may dissociate from the mTORC1 complex before TSC2 stimulates hydrolysis of GTP; TSC2 may not have access to critical residues of RHEB when present inside mTORC1.12820960Pubmed2003Insulin activation of Rheb, a mediator of mTOR/S6K/4E-BP signaling, is inhibited by TSC1 and 2Garami, AttilaZwartkruis, Fried J TNobukuni, TakahiroJoaquin, ManelRoccio, MartaStocker, HugoKozma, Sara CHafen, ErnstBos, Johannes LThomas, GeorgeMol. Cell 11:1457-6612869586Pubmed2003Rheb GTPase is a direct target of TSC2 GAP activity and regulates mTOR signalingInoki, KLi, YXu, TGuan, KLGenes Dev 17:1829-3412906785Pubmed2003Tuberous sclerosis complex gene products, Tuberin and Hamartin, control mTOR signaling by acting as a GTPase-activating protein complex toward RhebTee, ARManning, BDRoux, PPCantley, Lewis CBlenis, JCurr Biol 13:1259-68LEFT-TO-RIGHTSESN1,2,3 bind AMPKThis event has been computationally inferred from an event that has been demonstrated in another species.<p>The inference is based on the homology mapping from PANTHER. Briefly, reactions for which all involved PhysicalEntities (in input, output and catalyst) have a mapped orthologue/paralogue (for complexes at least 75% of components must have a mapping) are inferred to the other species. High level events are also inferred for these events to allow for easier navigation.<p><a href='/electronic_inference_compara.html' target = 'NEW'>More details and caveats of the event inference in Reactome.</a> For details on PANTHER see also: <a href='http://www.pantherdb.org/about.jsp' target='NEW'>http://www.pantherdb.org/about.jsp</a>p-AMPK heterotrimer:AMPReactome DB_ID: 10433135AMPadenosine 5'-monophosphateAdenylic acidAdenylate5'-AMP5'-Adenylic acid5'-Adenosine monophosphateAdenosine 5'-phosphateReactome DB_ID: 76577adenosine 5'-monophosphate [ChEBI:16027]adenosine 5'-monophosphateChEBICHEBI:16027Reactome Database ID Release 7576577Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=76577ReactomeR-ALL-765774Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-ALL-76577.4COMPOUNDC000201p-AMPK heterotrimerReactome DB_ID: 10427265Converted from EntitySet in ReactomeAMPK gammaReactome DB_ID: 10427253PRKAG1PRKAG1A0A1D5PPC7Reactome DB_ID: 10427245UniProt:A0A1D5PPC7PRKAG1UniProtA0A1D5PPC71EQUAL331EQUALReactome Database ID Release 7510427245Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10427245ReactomeR-GGA-3809461Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-GGA-380946.1PRKAG2PRKAG2F1NXL4Reactome DB_ID: 10427247UniProt:F1NXL4PRKAG2UniProtF1NXL41EQUAL569EQUALReactome Database ID Release 7510427247Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10427247ReactomeR-GGA-2004191Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-GGA-200419.1PRKAG3PRKAG3F1P1P1Reactome DB_ID: 10427251UniProt:F1P1P1PRKAG3UniProtF1P1P11EQUAL489EQUALReactome Database ID Release 7510427251Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10427251ReactomeR-GGA-3818391Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-GGA-381839.1Reactome Database ID Release 7510427253Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10427253ReactomeR-GGA-3818511Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-GGA-381851.11Converted from EntitySet in ReactomeAMPK betaReactome DB_ID: 10427241PRKAB1Q27IP4Reactome DB_ID: 10427237UniProt:Q27IP4UniProtQ27IP42EQUAL270EQUALReactome Database ID Release 7510427237Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10427237ReactomeR-GGA-3809681Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-GGA-380968.1PRKAB2PRKAB2Q156C7Reactome DB_ID: 10427239UniProt:Q156C7PRKAB2UniProtQ156C71EQUAL272EQUALReactome Database ID Release 7510427239Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10427239ReactomeR-GGA-2004131Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-GGA-200413.1Reactome Database ID Release 7510427241Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10427241ReactomeR-GGA-3818541Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-GGA-381854.11Converted from EntitySet in Reactomep-AMPK alphaReactome DB_ID: 10427263Q2LAI0phospho-p-T172-PRKAA2Reactome DB_ID: 10427258UniProt:Q2LAI0UniProtQ2LAI0172EQUALO-phospho-L-threonineMODMOD:000471EQUAL552EQUALReactome Database ID Release 7510427258Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10427258ReactomeR-GGA-2004171Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-GGA-200417.1Q2PUH1phospho-PRKAA1p-T183-PRKAA1Reactome DB_ID: 10427261UniProt:Q2PUH1PRKAA1UniProtQ2PUH1183EQUAL1EQUAL559EQUALReactome Database ID Release 7510427261Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10427261ReactomeR-GGA-3809641Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-GGA-380964.1Reactome Database ID Release 7510427263Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10427263ReactomeR-GGA-3818441Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-GGA-381844.11Reactome Database ID Release 7510427265Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10427265ReactomeR-GGA-3809341Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-GGA-380934.11Reactome Database ID Release 7510433135Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10433135ReactomeR-GGA-3809311Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-GGA-380931.1SESN1,2,3:p-AMPK heterotrimer:AMPReactome DB_ID: 1046464411Reactome Database ID Release 7510464644Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10464644ReactomeR-GGA-56319391Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-GGA-5631939.1Reactome Database ID Release 7510464646Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10464646ReactomeR-GGA-56319411Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-GGA-5631941.1SESN1, SESN2 and possibly SESN3 are able to bind the AMPK complex and increase its catalytic activity. The exact mechanism has not been elucidated, but recent studies suggest that sestrin-bound AMPK is resistant to inactivation through AKT-induced dephosphorylation (Budanov and Karin 2008, Sanli et al. 2012, Cam et al. 2014).18692468Pubmed2008p53 target genes sestrin1 and sestrin2 connect genotoxic stress and mTOR signalingBudanov, Andrei VKarin, MCell 134:451-6022363791Pubmed2012Sestrin2 modulates AMPK subunit expression and its response to ionizing radiation in breast cancer cellsSanli, ToranLinher-Melville, KatjaTsakiridis, TheodorosSingh, GurmitPLoS ONE 7:e3203524366874Pubmed2014p53/TAp63 and AKT regulate mammalian target of rapamycin complex 1 (mTORC1) signaling through two independent parallel pathways in the presence of DNA damageCam, MarenBid, Hemant KXiao, LinlinZambetti, Gerard PHoughton, Peter JCam, HakanJ. Biol. Chem. 289:4083-94LEFT-TO-RIGHT2.7.11AKT phosphorylates TSC2, inhibiting itThis event has been computationally inferred from an event that has been demonstrated in another species.<p>The inference is based on the homology mapping from PANTHER. Briefly, reactions for which all involved PhysicalEntities (in input, output and catalyst) have a mapped orthologue/paralogue (for complexes at least 75% of components must have a mapping) are inferred to the other species. High level events are also inferred for these events to allow for easier navigation.<p><a href='/electronic_inference_compara.html' target = 'NEW'>More details and caveats of the event inference in Reactome.</a> For details on PANTHER see also: <a href='http://www.pantherdb.org/about.jsp' target='NEW'>http://www.pantherdb.org/about.jsp</a>ATPAdenosine 5'-triphosphateATP(4-)Reactome DB_ID: 113592ATP(4-) [ChEBI:30616]ATP(4-)ATPatpAdenosine 5'-triphosphateChEBICHEBI:30616Reactome Database ID Release 75113592Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=113592ReactomeR-ALL-1135924Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-ALL-113592.4COMPOUNDC000022TSC2F1NGI4Reactome DB_ID: 10421947UniProt:F1NGI4UniProtF1NGI41EQUAL1807EQUALReactome Database ID Release 7510421947Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10421947ReactomeR-GGA-29805481Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-GGA-2980548.1ADPAdenosine 5'-diphosphateADP(3-)Reactome DB_ID: 29370ADP(3-) [ChEBI:456216]ADP(3-)ADP5&apos;-O-[(phosphonatooxy)phosphinato]adenosineADP trianionChEBICHEBI:456216Reactome Database ID Release 7529370Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=29370ReactomeR-ALL-293704Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-ALL-29370.4COMPOUNDC000082F1NGI4phospho-p-S939,T1462-TSC2Reactome DB_ID: 10426237939EQUALO-phospho-L-serineMODMOD:000461462EQUAL1EQUAL1807EQUALReactome Database ID Release 7510426237Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10426237ReactomeR-GGA-1994841Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-GGA-199484.1ACTIVATIONactiveUnit: #Protein39A0A3Q2U4X3phospho-p-T308,S473-AKT1Reactome DB_ID: 10426175UniProt:A0A3Q2U4X3UniProtA0A3Q2U4X3308EQUAL473EQUAL1EQUAL480EQUALReactome Database ID Release 7510426175Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10426175ReactomeR-GGA-1983561Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-GGA-198356.1GENE ONTOLOGYGO:0004674Reactome Database ID Release 7510426233Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10426233Reactome Database ID Release 7510426239Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10426239ReactomeR-GGA-1986091Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-GGA-198609.1GENE ONTOLOGYGO:0043491gene ontology term for cellular processMIMI:0359AKT phosphorylates and inhibits TSC2 (tuberin), a suppressor of the TOR kinase pathway, which senses nutrient levels in the environment. TSC2 forms a protein complex with TSC1 and this complex acts as a GAP (GTPase activating protein) for the RHEB G-protein. RHEB, in turn, activates the TOR kinase. Thus, an active AKT1 activates the TOR kinase, both of which are positive signals for cell growth (an increase in cell mass) and division.<br>The TOR kinase regulates two major processes: translation of selected mRNAs in the cell and autophagy. In the presence of high nutrient levels TOR is active and phosphorylates the 4EBP protein releasing the eukaryotic initiation factor 4E (eIF4E), which is essential for cap-dependent initiation of translation and promoting growth of the cell (PMID: 15314020). TOR also phosphorylates the S6 kinase, which is implicated in ribosome biogenesis as well as in the modification of the S6 ribosomal protein. AKT can also activate mTOR by another mechanism, involving phosphorylation of PRAS40, an inhibitor of mTOR activity.12172553Pubmed2002TSC2 is phosphorylated and inhibited by Akt and suppresses mTOR signallingInoki, KLi, YunZhu, TWu, JGuan, KLNat Cell Biol 4:648-5712150915Pubmed2002Identification of the tuberous sclerosis complex-2 tumor suppressor gene product tuberin as a target of the phosphoinositide 3-kinase/akt pathwayManning, BDTee, ARLogsdon, MNBlenis, JCantley, Lewis CMol Cell 10:151-62LEFT-TO-RIGHTp-S939,T1462-TSC2 binding to 14-3-3 dimer is negatively regulated by DDIT4This event has been computationally inferred from an event that has been demonstrated in another species.<p>The inference is based on the homology mapping from PANTHER. Briefly, reactions for which all involved PhysicalEntities (in input, output and catalyst) have a mapped orthologue/paralogue (for complexes at least 75% of components must have a mapping) are inferred to the other species. High level events are also inferred for these events to allow for easier navigation.<p><a href='/electronic_inference_compara.html' target = 'NEW'>More details and caveats of the event inference in Reactome.</a> For details on PANTHER see also: <a href='http://www.pantherdb.org/about.jsp' target='NEW'>http://www.pantherdb.org/about.jsp</a>Converted from EntitySet in Reactome14-3-3 dimerReactome DB_ID: 1046466814-3-3 eta dimerReactome DB_ID: 10464652YWHAHYWHAHQ5ZKJ2Reactome DB_ID: 10464650UniProt:Q5ZKJ2YWHAHUniProtQ5ZKJ22EQUAL246EQUALReactome Database ID Release 7510464650Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10464650ReactomeR-GGA-14451071Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-GGA-1445107.12Reactome Database ID Release 7510464652Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10464652ReactomeR-GGA-22627151Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-GGA-2262715.1YWHAG dimerReactome DB_ID: 10464654YWHAGF1NMY1Reactome DB_ID: 10432896UniProt:F1NMY1UniProtF1NMY11EQUAL247EQUALReactome Database ID Release 7510432896Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10432896ReactomeR-GGA-3803121Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-GGA-380312.12Reactome Database ID Release 7510464654Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10464654ReactomeR-GGA-22627131Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-GGA-2262713.1SFN dimerReactome DB_ID: 10464660SFNSFNR4GF89Reactome DB_ID: 10464658UniProt:R4GF89SFNUniProtR4GF891EQUAL248EQUALReactome Database ID Release 7510464658Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10464658ReactomeR-GGA-14451051Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-GGA-1445105.12Reactome Database ID Release 7510464660Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10464660ReactomeR-GGA-22627161Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-GGA-2262716.1YWHAQ dimerReactome DB_ID: 10464666YWHAQYWHAQQ5ZMD1Reactome DB_ID: 10464664UniProt:Q5ZMD1YWHAQUniProtQ5ZMD11EQUAL245EQUALReactome Database ID Release 7510464664Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10464664ReactomeR-GGA-14451161Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-GGA-1445116.12Reactome Database ID Release 7510464666Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10464666ReactomeR-GGA-22627141Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-GGA-2262714.1YWHAZ dimerReactome DB_ID: 10437110YWHAZYWHAZQ5ZKC9Reactome DB_ID: 10434201UniProt:Q5ZKC9YWHAZUniProtQ5ZKC91EQUAL245EQUALReactome Database ID Release 7510434201Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10434201ReactomeR-GGA-2060991Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-GGA-206099.12Reactome Database ID Release 7510437110Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10437110ReactomeR-GGA-2067511Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-GGA-206751.1YWHAB dimerReactome DB_ID: 10452152YWHABYWHABQ5ZLQ6Reactome DB_ID: 10422053UniProt:Q5ZLQ6YWHABUniProtQ5ZLQ61EQUAL246EQUALReactome Database ID Release 7510422053Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10422053ReactomeR-GGA-488881Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-GGA-48888.12Reactome Database ID Release 7510452152Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10452152ReactomeR-GGA-20286451Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-GGA-2028645.1Reactome Database ID Release 7510464668Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10464668ReactomeR-GGA-14451381Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-GGA-1445138.1p-S939,T1462-TSC2:14-3-3 dimerReactome DB_ID: 1046467011Reactome Database ID Release 7510464670Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10464670ReactomeR-GGA-56327271Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-GGA-5632727.1Reactome Database ID Release 7510464678Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10464678ReactomeR-GGA-56327321Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-GGA-5632732.1Phosphorylation of TSC2 by AKT enables association of TSC2 with 14-3-3 proteins YWHAB (14-3-3 protein beta/alpha), YWHAQ (14-3-3 protein theta), YWHAG (14-3-3 protein gamma), YWHAH (14-3-3 protein eta), YWHAE (14-3-3 protein epsilon), YWHAZ (14-3-3 protein zeta/delta) or SFN (14-3-3 protein sigma) (Liu et al. 2002). Binding to 14-3-3 proteins sequesters TSC2 to the cytosol and prevents its association with TSC1 (Cai et al. 2006).12438239Pubmed200214-3-3 interacts with the tumor suppressor tuberin at Akt phosphorylation site(s)Liu, Matt YCai, ShengliEspejo, AlexsandraBedford, Mark TWalker, Cheryl LynCancer Res. 62:6475-8016636147Pubmed2006Activity of TSC2 is inhibited by AKT-mediated phosphorylation and membrane partitioningCai, Sheng-LiTee, Andrew RShort, John DBergeron, Judith MKim, JinheeShen, JianjunGuo, RuifengJohnson, Charles LKiguchi, KaoruWalker, Cheryl LynJ. Cell Biol. 173:279-89INHIBITIONReactome Database ID Release 7510464679Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10464679DDIT4:14-3-3 dimerReactome DB_ID: 10464676DDIT4A0A1D5PRJ4Reactome DB_ID: 10464674UniProt:A0A1D5PRJ4UniProtA0A1D5PRJ41EQUAL232EQUALReactome Database ID Release 7510464674Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10464674ReactomeR-GGA-56323741Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-GGA-5632374.111Reactome Database ID Release 7510464676Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10464676ReactomeR-GGA-56327411Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-GGA-5632741.1LEFT-TO-RIGHTDDIT4 binds 14-3-3 dimerThis event has been computationally inferred from an event that has been demonstrated in another species.<p>The inference is based on the homology mapping from PANTHER. Briefly, reactions for which all involved PhysicalEntities (in input, output and catalyst) have a mapped orthologue/paralogue (for complexes at least 75% of components must have a mapping) are inferred to the other species. High level events are also inferred for these events to allow for easier navigation.<p><a href='/electronic_inference_compara.html' target = 'NEW'>More details and caveats of the event inference in Reactome.</a> For details on PANTHER see also: <a href='http://www.pantherdb.org/about.jsp' target='NEW'>http://www.pantherdb.org/about.jsp</a>Reactome Database ID Release 7510464681Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10464681ReactomeR-GGA-56327381Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-GGA-5632738.1DDIT4 (REDD1) binds 14-3-3 proteins through a conserved 14-3-3 binding motif Arg-X-X-X-Ser/Thr-X-Pro (DeYoung et al. 2008). Binding of DDIT4 to 14-3-3 proteins competes with 14-3-3 binding to TSC2 and thus prevents AKT-mediated inactivation of TSC2 (Cam et al. 2014).18198340Pubmed2008Hypoxia regulates TSC1/2-mTOR signaling and tumor suppression through REDD1-mediated 14-3-3 shuttlingDeYoung, Maurice PhillipHorak, PeterSofer, AviSgroi, DennisEllisen, Leif WGenes Dev. 22:239-51LEFT-TO-RIGHT1.9.3.1Electron transfer from reduced cytochrome c to molecular oxygenThis event has been computationally inferred from an event that has been demonstrated in another species.<p>The inference is based on the homology mapping from PANTHER. Briefly, reactions for which all involved PhysicalEntities (in input, output and catalyst) have a mapped orthologue/paralogue (for complexes at least 75% of components must have a mapping) are inferred to the other species. High level events are also inferred for these events to allow for easier navigation.<p><a href='/electronic_inference_compara.html' target = 'NEW'>More details and caveats of the event inference in Reactome.</a> For details on PANTHER see also: <a href='http://www.pantherdb.org/about.jsp' target='NEW'>http://www.pantherdb.org/about.jsp</a>Cytochrome c (reduced)Reactome DB_ID: 10421332mitochondrial inner membraneGENE ONTOLOGYGO:0005743ferrohemeReactome DB_ID: 3341317ferroheme [ChEBI:38573]ferrohemeferrohaemChEBICHEBI:38573Reactome Database ID Release 753341317Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=3341317ReactomeR-ALL-33413172Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-ALL-3341317.21Converted from EntitySet in ReactomeHomologues of CYCSReactome DB_ID: 10421330CYCSA0A1D5P4L5Reactome DB_ID: 10421326UniProt:A0A1D5P4L5UniProtA0A1D5P4L52EQUAL105EQUALReactome Database ID Release 7510421326Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10421326ReactomeR-GGA-3526081Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-GGA-352608.1CYCCYCSP67881Reactome DB_ID: 10421328UniProt:P67881CYCUniProtP678812EQUAL105EQUALReactome Database ID Release 7510421328Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10421328ReactomeR-GGA-352608-21Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-GGA-352608-2.1Reactome Database ID Release 7510421330Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10421330ReactomeR-GGA-352608-31Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-GGA-352608-3.11Reactome Database ID Release 7510421332Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10421332ReactomeR-GGA-3526091Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-GGA-352609.14H+hydronReactome DB_ID: 113529mitochondrial matrixGENE ONTOLOGYGO:0005759Reactome Database ID Release 75113529Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=113529ReactomeR-ALL-1135294Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-ALL-113529.4COMPOUNDC0008012O2OxygendioxygenReactome DB_ID: 113533dioxygen [ChEBI:15379]dioxygenChEBICHEBI:15379Reactome Database ID Release 75113533Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=113533ReactomeR-ALL-1135333Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-ALL-113533.3COMPOUNDC00007H+hydronReactome DB_ID: 163953mitochondrial intermembrane spaceGENE ONTOLOGYGO:0005758Reactome Database ID Release 75163953Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=163953ReactomeR-ALL-1639533Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-ALL-163953.3COMPOUNDC000808H2OwaterReactome DB_ID: 113521Reactome Database ID Release 75113521Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=113521ReactomeR-ALL-1135213Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-ALL-113521.3COMPOUNDC000012Cytochrome c (oxidised)Reactome DB_ID: 10421334ferrihemeReactome DB_ID: 3341371ferriheme [ChEBI:38574]ferrihemeferrihaemChEBICHEBI:38574Reactome Database ID Release 753341371Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=3341371ReactomeR-ALL-33413712Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-ALL-3341371.211Reactome Database ID Release 7510421334Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10421334ReactomeR-GGA-3526071Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-GGA-352607.14ACTIVATIONCytochrome c oxidaseReactome DB_ID: 10421388COX8AA0A1L1RQ94Reactome DB_ID: 10421338UniProt:A0A1L1RQ94UniProtA0A1L1RQ9426EQUAL69EQUALReactome Database ID Release 7510421338Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10421338ReactomeR-GGA-1643131Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-GGA-164313.11COX4I1COX4I1Q5ZJV5Reactome DB_ID: 10421378UniProt:Q5ZJV5COX4I1UniProtQ5ZJV523EQUAL169EQUALReactome Database ID Release 7510421378Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10421378ReactomeR-GGA-1643051Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-GGA-164305.11MT-CO1MT-CO1P18943Reactome DB_ID: 10421366UniProt:P18943MT-CO1UniProtP189431EQUAL513EQUALReactome Database ID Release 7510421366Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10421366ReactomeR-GGA-1643141Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-GGA-164314.11COX7BF1NL83Reactome DB_ID: 10421342UniProt:F1NL83UniProtF1NL8325EQUAL80EQUALReactome Database ID Release 7510421342Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10421342ReactomeR-GGA-1643091Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-GGA-164309.11NDUFA4A0A1L1RIQ5Reactome DB_ID: 10421386UniProt:A0A1L1RIQ5UniProtA0A1L1RIQ51EQUAL81EQUALReactome Database ID Release 7510421386Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10421386ReactomeR-GGA-606171Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-GGA-60617.11MT-CO3MT-CO3P18945Reactome DB_ID: 10421374UniProt:P18945MT-CO3UniProtP189452EQUAL261EQUALReactome Database ID Release 7510421374Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10421374ReactomeR-GGA-1643121Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-GGA-164312.11COX7CR4GLP0Reactome DB_ID: 10421346UniProt:R4GLP0UniProtR4GLP017EQUAL63EQUALReactome Database ID Release 7510421346Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10421346ReactomeR-GGA-1643061Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-GGA-164306.11MT-CO2:CuAReactome DB_ID: 10421382CuACopper Acopper atomReactome DB_ID: 164300copper atom [ChEBI:28694]copper atomCucopper29CucuprumcuivreKupfercobreCopperChEBICHEBI:28694Reactome Database ID Release 75164300Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=164300ReactomeR-ALL-1643003Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-ALL-164300.3COMPOUNDC000701MT-CO2MT-CO2P18944Reactome DB_ID: 10421370UniProt:P18944MT-CO2UniProtP189441EQUAL227EQUALReactome Database ID Release 7510421370Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10421370ReactomeR-GGA-1643021Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-GGA-164302.11Reactome Database ID Release 7510421382Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10421382ReactomeR-GGA-1643031Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-GGA-164303.11Ghost homologue of COX6B1Reactome DB_ID: 10421352Reactome Database ID Release 7510421352Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10421352ReactomeR-GGA-1642991Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-GGA-164299.11Ghost homologue of COX6C(3-75)Reactome DB_ID: 10421354Reactome Database ID Release 7510421354Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10421354ReactomeR-GGA-1642981Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-GGA-164298.11COX5AE1C043Reactome DB_ID: 10421358UniProt:E1C043UniProtE1C04342EQUAL150EQUALReactome Database ID Release 7510421358Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10421358ReactomeR-GGA-1643081Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-GGA-164308.11COX6A1A0A1L1RSG1Reactome DB_ID: 10421350UniProt:A0A1L1RSG1UniProtA0A1L1RSG125EQUAL109EQUALReactome Database ID Release 7510421350Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10421350ReactomeR-GGA-1643011Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-GGA-164301.111COX5BA0A1D5PUI6Reactome DB_ID: 10421362UniProt:A0A1D5PUI6UniProtA0A1D5PUI632EQUAL129EQUALReactome Database ID Release 7510421362Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10421362ReactomeR-GGA-1643071Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-GGA-164307.11Ghost homologue of COX7A2LReactome DB_ID: 10421380Reactome Database ID Release 7510421380Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10421380ReactomeR-GGA-1643101Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-GGA-164310.11Reactome Database ID Release 7510421388Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10421388ReactomeR-GGA-1643161Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-GGA-164316.1GENE ONTOLOGYGO:0004129Reactome Database ID Release 7510421389Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10421389Reactome Database ID Release 7510421431Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10421431ReactomeR-GGA-1632141Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-GGA-163214.1GENE ONTOLOGYGO:0006123Complex IV (COX, cytochrome c oxidase) contains the hemeprotein cytochrome a and a3. It also contains copper atoms which undergo a transition from Cu+ to Cu2+ during the transfer of electrons through the complex to molecular oxygen. A bimetallic centre containing a copper atom and a heme-linked iron protein binds oxygen after 4 electrons have been picked up. Water, the final product of oxygen reduction, is then released. Oxygen is the final electron acceptor in the respiratory chain. The overall reaction can be summed as<br><br>4Cyt c (red.) + 12H+ (in) + O2 = 4Cyt c (ox.) + 2H2O + 8H+ (out)<br><br>Four protons are taken up from the matrix side of the membrane to form the water (scalar protons). Wikstrom (1977) suggests 4 protons are additionally transferred out from the matrix to the intermembrane space.<br><br>COX ancillary proteins mediate membrane insertion, catalytic core processing, copper transport and insertion into core subunits and heme A biosynthesis (Stilburek et al. 2006, Fontanesi et al. 2006, Soto et al. 2012). To date, all Mendelian disorders presenting COX deficiency have been assigned to mutations in ancillary factors, with the exception of an infantile encephalomyopathy caused by a defective COX6B1 and an exocrine pancreatic insufficiency caused by a defective COX4I2 gene (Soto et al. 2012). Balsa et al have shown that NDUFA4, formerly considered to be a constituent of NADH dehydrogenase (Complex I), is instead a component of the cytochrome c oxidase (CIV) (Balsa et al. 2012). Patients with NDUFA4 mutations display COX deficiencies (Pitceathly et al. 2013).7979252Pubmed1994Energy transduction by cytochrome complexes in mitochondrial and bacterialTrumpower, BLGennis, RBAnnu Rev Biochem 63:675-71611340051Pubmed2001Structures and proton-pumping strategies of mitochondrial respiratorySchultz, BEChan, SIAnnu Rev Biophys Biomol Struct 30:23-6521958598Pubmed2012Biogenesis and assembly of eukaryotic cytochrome c oxidase catalytic coreSoto, Ileana CFontanesi, FlaviaLiu, JingjingBarrientos, AntoniBiochim. Biophys. Acta 1817:883-9722902835Pubmed2012NDUFA4 is a subunit of complex IV of the mammalian electron transport chainBalsa, EduardoMarco, RicardoPerales-Clemente, EsterSzklarczyk, RadekCalvo, EnriqueLandázuri, Manuel OEnríquez, José AntonioCell Metab. 16:378-8617298220Pubmed2006Biogenesis of eukaryotic cytochrome c oxidaseStiburek, LHansikova, HTesarova, MCerna, LZeman, JPhysiol Res 55:S27-4123746447Pubmed2013NDUFA4 mutations underlie dysfunction of a cytochrome c oxidase subunit linked to human neurological diseasePitceathly, Robert D SRahman, SWedatilake, YehaniPolke, James MCirak, SebahattinFoley, A ReghanSailer, AnnaHurles, Matthew EStalker, JimHargreaves, IainWoodward, Cathy ESweeney, Mary GMuntoni, FrancescoHoulden, HenryTaanman, Jan-WillemHanna, Michael GCell Rep 3:1795-80515223Pubmed1977Proton pump coupled to cytochrome c oxidase in mitochondriaWikstrom, MKNature 266:271-316760263Pubmed2006Assembly of mitochondrial cytochrome c-oxidase, a complicated and highly regulated cellular processFontanesi, FlaviaSoto, Ileana CHorn, DarrylBarrientos, AntoniAm. J. Physiol., Cell Physiol. 291:C1129-47ACTIVATIONReactome Database ID Release 7510421433Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10421433Converted from EntitySet in ReactomeCOX11,14,16,18,20Reactome DB_ID: 10421411COX11R4GL85Reactome DB_ID: 10421397UniProt:R4GL85UniProtR4GL851EQUAL276EQUALReactome Database ID Release 7510421397Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10421397ReactomeR-GGA-53361551Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-GGA-5336155.1COX16COX16E1C6R2Reactome DB_ID: 10421401UniProt:E1C6R2COX16UniProtE1C6R21EQUAL106EQUALReactome Database ID Release 7510421401Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10421401ReactomeR-GGA-53361351Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-GGA-5336135.1COX20A0A1D5PAK5Reactome DB_ID: 10421405UniProt:A0A1D5PAK5UniProtA0A1D5PAK51EQUAL118EQUALReactome Database ID Release 7510421405Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10421405ReactomeR-GGA-53361691Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-GGA-5336169.1COX18F1P5L3Reactome DB_ID: 10421409UniProt:F1P5L3UniProtF1P5L31EQUAL333EQUALReactome Database ID Release 7510421409Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10421409ReactomeR-GGA-52161901Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-GGA-5216190.1Reactome Database ID Release 7510421411Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10421411ReactomeR-GGA-53361431Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-GGA-5336143.1ACTIVATIONReactome Database ID Release 7510421432Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10421432COX19R4GKS3Reactome DB_ID: 10421393UniProt:R4GKS3UniProtR4GKS32EQUAL90EQUALReactome Database ID Release 7510421393Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10421393ReactomeR-GGA-68000711Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-GGA-6800071.1ACTIVATIONReactome Database ID Release 7510421434Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10421434Converted from EntitySet in ReactomeCOX ancilliary proteinsReactome DB_ID: 10421429LRPPRCLRPPRCF1NGU3Reactome DB_ID: 10421415UniProt:F1NGU3LRPPRCUniProtF1NGU360EQUAL1394EQUALReactome Database ID Release 7510421415Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10421415ReactomeR-GGA-53361741Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-GGA-5336174.1SCO1SCO1A0A3Q2UP04Reactome DB_ID: 10421419UniProt:A0A3Q2UP04SCO1UniProtA0A3Q2UP041EQUAL301EQUALReactome Database ID Release 7510421419Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10421419ReactomeR-GGA-53361701Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-GGA-5336170.1SCO2SCO2A0A3Q2U072Reactome DB_ID: 10421423UniProt:A0A3Q2U072SCO2UniProtA0A3Q2U07242EQUAL266EQUALReactome Database ID Release 7510421423Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10421423ReactomeR-GGA-53361501Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-GGA-5336150.1SURF1SURF1Q800L1Reactome DB_ID: 10421427UniProt:Q800L1SURF1UniProtQ800L11EQUAL300EQUALReactome Database ID Release 7510421427Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10421427ReactomeR-GGA-53361591Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-GGA-5336159.1Reactome Database ID Release 7510421429Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10421429ReactomeR-GGA-55664881Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-GGA-5566488.1LEFT-TO-RIGHT3.5.1.2glutamine + H2O => glutamate + NH4+ [GLS]This event has been computationally inferred from an event that has been demonstrated in another species.<p>The inference is based on the homology mapping from PANTHER. Briefly, reactions for which all involved PhysicalEntities (in input, output and catalyst) have a mapped orthologue/paralogue (for complexes at least 75% of components must have a mapping) are inferred to the other species. High level events are also inferred for these events to allow for easier navigation.<p><a href='/electronic_inference_compara.html' target = 'NEW'>More details and caveats of the event inference in Reactome.</a> For details on PANTHER see also: <a href='http://www.pantherdb.org/about.jsp' target='NEW'>http://www.pantherdb.org/about.jsp</a>L-GlnL-2-Aminoglutaramic acidL-glutamine zwitterionL-glutamineReactome DB_ID: 113522L-glutamine zwitterion [ChEBI:58359]L-glutamine zwitterion146.14450(2S)-5-amino-2-ammonio-5-oxopentanoateNC(=O)CC[C@H]([NH3+])C([O-])=OC5H10N2O3(2S)-5-amino-2-azaniumyl-5-oxopentanoateL-glutamineZDXPYRJPNDTMRX-VKHMYHEASA-NInChI=1S/C5H10N2O3/c6-3(5(9)10)1-2-4(7)8/h3H,1-2,6H2,(H2,7,8)(H,9,10)/t3-/m0/s1ChEBICHEBI:58359Reactome Database ID Release 75113522Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=113522ReactomeR-ALL-1135224Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-ALL-113522.4COMPOUNDC00064GluL-GluL-glutamate(1-)L-glutamic acidL-GlutamateL-Glutaminic acidReactome DB_ID: 113552L-glutamate(1-) [ChEBI:29985]L-glutamate(1-)L-glutamic acid, ion(1-)[NH3+][C@@H](CCC([O-])=O)C([O-])=OWHUUTDBJXJRKMK-VKHMYHEASA-MC5H8NO4146.12136(2S)-2-ammoniopentanedioatehydrogen L-glutamateL-glutamateL-glutamic acid monoanionInChI=1S/C5H9NO4/c6-3(5(9)10)1-2-4(7)8/h3H,1-2,6H2,(H,7,8)(H,9,10)/p-1/t3-/m0/s1ChEBICHEBI:29985Reactome Database ID Release 75113552Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=113552ReactomeR-ALL-1135525Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-ALL-113552.5COMPOUNDC00025NH4+ammoniumReactome DB_ID: 113561ammonium [ChEBI:28938]ammoniumChEBICHEBI:28938Reactome Database ID Release 75113561Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=113561ReactomeR-ALL-1135613Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-ALL-113561.3COMPOUNDC01342ACTIVATIONGLS dimerReactome DB_ID: 10414121GLSGLS2A0A1D5PNV1Reactome DB_ID: 10414119UniProt:A0A1D5PNV1GLS2UniProtA0A1D5PNV117EQUAL669EQUALReactome Database ID Release 7510414119Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10414119ReactomeR-GGA-706071Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-GGA-70607.12Reactome Database ID Release 7510414121Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10414121ReactomeR-GGA-5078601Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-GGA-507860.1GENE ONTOLOGYGO:0004359Reactome Database ID Release 7510414122Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10414122Reactome Database ID Release 7510414124Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10414124ReactomeR-GGA-706091Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-GGA-70609.1Mitochondrial glutaminase (GLS) catalyzes the hydrolysis of glutamine to yield glutamate and ammonia. Two GLS enzymes have been identified, one abundantly expressed in the liver (GLS - Elgadi et al. 1999) and one abundantly expressed in kidney (GLS2 - Gomez-Fabre et al. 2000). Their biochemical properties are similar. The enzymes are inferred to function as dimers based on unpublished crystallographic data for GLS (PDB 3CZD) and studies of glutaminase enzyme purified from Ehrlich Ascites cells (Quesada et al. 1988).11015561Pubmed1999Cloning and analysis of unique human glutaminase isoforms generated by tissue-specific alternative splicingElgadi, KMMeguid, RAQian, MSouba, WWAbcouwer, SFPhysiol Genomics 1:51-6210620514Pubmed2000Molecular cloning, sequencing and expression studies of the human breast cancer cell glutaminaseGomez-Fabre, PMAledo, JCDel Castillo-Olivares, AAlonso, FJNunez De Castro, ICampos, JAMarquez, JBiochem J 345:365-753214421Pubmed1988Purification of phosphate-dependent glutaminase from isolated mitochondria of Ehrlich ascites-tumour cellsQuesada, ARSánchez-Jiménez, FPerez-Rodriguez, JMarquez, JMedina, MANunez De Castro, IBiochem J 255:1031-5Reactome Database ID Release 7510487876Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10487876ReactomeR-GGA-56288971Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-GGA-5628897.1While the p53 tumor suppressor protein (TP53) is known to inhibit cell growth by inducing apoptosis, senescence and cell cycle arrest, recent studies have found that p53 is also able to influence cell metabolism to prevent tumor development. TP53 regulates transcription of many genes involved in the metabolism of carbohydrates, nucleotides and amino acids, protein synthesis and aerobic respiration.<p>TP53 stimulates transcription of TIGAR, a D-fructose 2,6-bisphosphatase. TIGAR activity decreases glycolytic rate and lowers ROS (reactive oxygen species) levels in cells (Bensaad et al. 2006). TP53 may also negatively regulate the rate of glycolysis by inhibiting the expression of glucose transporters GLUT1, GLUT3 and GLUT4 (Kondoh et al. 2005, Schwartzenberg-Bar-Yoseph et al. 2004, Kawauchi et al. 2008).<p>TP53 negatively regulates several key points in PI3K/AKT signaling and downstream mTOR signaling, decreasing the rate of protein synthesis and, hence, cellular growth. TP53 directly stimulates transcription of the tumor suppressor PTEN, which acts to inhibit PI3K-mediated activation of AKT (Stambolic et al. 2001). TP53 stimulates transcription of sestrin genes, SESN1, SESN2, and SESN3 (Velasco-Miguel et al. 1999, Budanov et al. 2002, Brynczka et al. 2007). One of sestrin functions may be to reduce and reactivate overoxidized peroxiredoxin PRDX1, thereby reducing ROS levels (Budanov et al. 2004, Papadia et al. 2008, Essler et al. 2009). Another function of sestrins is to bind the activated AMPK complex and protect it from AKT-mediated inactivation. By enhancing AMPK activity, sestrins negatively regulate mTOR signaling (Budanov and Karin 2008, Cam et al. 2014). The expression of DDIT4 (REDD1), another negative regulator of mTOR signaling, is directly stimulated by TP63 and TP53. DDIT4 prevents AKT-mediated inactivation of TSC1:TSC2 complex, thus inhibiting mTOR cascade (Cam et al. 2014, Ellisen et al. 2002, DeYoung et al. 2008). TP53 may also be involved, directly or indirectly, in regulation of expression of other participants of PI3K/AKT/mTOR signaling, such as PIK3CA (Singh et al. 2002), TSC2 and AMPKB (Feng et al. 2007). <p>TP53 regulates mitochondrial metabolism through several routes. TP53 stimulates transcription of SCO2 gene, which encodes a mitochondrial cytochrome c oxidase assembly protein (Matoba et al. 2006). TP53 stimulates transcription of RRM2B gene, which encodes a subunit of the ribonucleotide reductase complex, responsible for the conversion of ribonucleotides to deoxyribonucleotides and essential for the maintenance of mitochondrial DNA content in the cell (Tanaka et al. 2000, Bourdon et al. 2007, Kulawiec et al. 2009). TP53 also transactivates mitochondrial transcription factor A (TFAM), a nuclear-encoded gene important for mitochondrial DNA (mtDNA) transcription and maintenance (Park et al. 2009). Finally, TP53 stimulates transcription of the mitochondrial glutaminase GLS2, leading to increased mitochondrial respiration rate and reduced ROS levels (Hu et al. 2010). <p>The great majority of tumor cells generate energy through aerobic glycolysis, rather than the much more efficient aerobic mitochondrial respiration, and this metabolic change is known as the Warburg effect (Warburg 1956). Since the majority of tumor cells have impaired TP53 function, and TP53 regulates a number of genes involved in glycolysis and mitochondrial respiration, it is likely that TP53 inactivation plays an important role in the metabolic derangement of cancer cells such as the Warburg effect and the concomitant increased tumorigenicity (reviewed by Feng and Levine 2010). On the other hand, some mutations of TP53 in Li-Fraumeni syndrome may result in the retention of its wild-type metabolic activities while losing cell cycle and apoptosis functions (Wang et al. 2013). Consistent with such human data, some mutations of p53, unlike p53 null state, retain the ability to regulate energy metabolism while being inactive in regulating its classic gene targets involved in cell cycle, apoptosis and senescence. Retention of metabolic and antioxidant functions of p53 protects p53 mutant mice from early onset tumorigenesis (Li et al. 2012). 15059920Pubmed2004The tumor suppressor p53 down-regulates glucose transporters GLUT1 and GLUT4 gene expressionSchwartzenberg-Bar-Yoseph, FabianaArmoni, MichalKarnieli, EddyCancer Res. 64:2627-3311545734Pubmed2001Regulation of PTEN transcription by p53Stambolic, VMacPherson, DSas, DLin, YSnow, BJang, YBenchimol, SMak, T WMol. Cell 8:317-2517540029Pubmed2007NGF-mediated transcriptional targets of p53 in PC12 neuronal differentiationBrynczka, ChristopherLabhart, PaulMerrick, B AlexBMC Genomics 8:13916728594Pubmed2006p53 regulates mitochondrial respirationMatoba, SatoakiKang, Ju-GyeongPatino, Willmar DWragg, AndrewBoehm, ManfredGavrilova, OksanaHurley, Paula JBunz, FredHwang, Paul MScience 312:1650-319439913Pubmed2009p53 regulates mtDNA copy number and mitocheckpoint pathwayKulawiec, MariolaAyyasamy, VanniarajanSingh, Keshav KJ Carcinog 8:817409411Pubmed2007The regulation of AMPK beta1, TSC2, and PTEN expression by p53: stress, cell and tissue specificity, and the role of these gene products in modulating the IGF-1-AKT-mTOR pathwaysFeng, ZhaohuiHu, Wenweide Stanchina, ETeresky, Angelika KJin, ShengkanLowe, SLevine, Arnold JCancer Res. 67:3043-5313298683Pubmed1956On the origin of cancer cellsWARBURG, OScience 123:309-1410716435Pubmed2000A ribonucleotide reductase gene involved in a p53-dependent cell-cycle checkpoint for DNA damageTanaka, HiroshiArakawa, HirofumiYamaguchi, TatsuyaShiraishi, KenjiFukuda, SeisukeMatsui, KunikoTakei, YoshikiNakamura, YusukeNature 404:42-4918391940Pubmed2008p53 regulates glucose metabolism through an IKK-NF-kappaB pathway and inhibits cell transformationKawauchi, KeikoAraki, KeigoTobiume, KeiTanaka, NobuyukiNat. Cell Biol. 10:611-89926927Pubmed1999PA26, a novel target of the p53 tumor suppressor and member of the GADD family of DNA damage and growth arrest inducible genesVelasco-Miguel, SBuckbinder, LJean, PGelbert, LTalbott, RLaidlaw, JSeizinger, BKley, NOncogene 18:127-3720399660Pubmed2010The regulation of energy metabolism and the IGF-1/mTOR pathways by the p53 proteinFeng, ZhaohuiLevine, Arnold JTrends Cell Biol. 20:427-3417486094Pubmed2007Mutation of RRM2B, encoding p53-controlled ribonucleotide reductase (p53R2), causes severe mitochondrial DNA depletionBourdon, AliceMinai, LimorSerre, ValérieJais, Jean-PhilippeSarzi, EmmanuelleAubert, SophieChrétien, Dominiquede Lonlay, PascalePaquis-Flucklinger, VeroniqueArakawa, HirofumiNakamura, YusukeMunnich, ARötig, AgnèsNat. Genet. 39:776-8011959846Pubmed2002p53 regulates cell survival by inhibiting PIK3CA in squamous cell carcinomasSingh, BReddy, Pabbathi GGoberdhan, AndyWalsh, ChristineDao, SuNgai, IvanChou, Ting ChaoO-Charoenrat, PornchaiLevine, Arnold JRao, Pulivarthi HStoffel, ArchontoulaGenes Dev. 16:984-9320378837Pubmed2010Glutaminase 2, a novel p53 target gene regulating energy metabolism and antioxidant functionHu, WenweiZhang, CenWu, RuiSun, YvonneLevine, ArnoldFeng, ZhaohuiProc. Natl. Acad. Sci. U.S.A. 107:7455-6015665293Pubmed2005Glycolytic enzymes can modulate cellular life spanKondoh, HiroshiLleonart, Matilde EGil, JesúsWang, JingDegan, PaoloPeters, GordonMartinez, DoloresCarnero, AmancioBeach, DavidCancer Res. 65:177-8512203114Pubmed2002Identification of a novel stress-responsive gene Hi95 involved in regulation of cell viabilityBudanov, Andrei VShoshani, TziporaFaerman, AlexanderZelin, ElenaKamer, IrisKalinski, HagarGorodin, SvetlanaFishman, AllaChajut, AyeletEinat, PazSkaliter, RamiGudkov, Andrei VChumakov, Peter MFeinstein, ElenaOncogene 21:6017-3112453409Pubmed2002REDD1, a developmentally regulated transcriptional target of p63 and p53, links p63 to regulation of reactive oxygen speciesEllisen, Leif WRamsayer, Kate DJohannessen, Cory MYang, AnnieBeppu, HideyukiMinda, KarolinaOliner, Jonathan DMcKeon, FrankHaber, Daniel AMol. Cell 10:995-100523484829Pubmed2013Increased oxidative metabolism in the Li-Fraumeni syndromeWang, Ping-yuanMa, WenzhePark, Joon-YoungCeli, Francesco SArena, RossChoi, Jeong WAli, Qais ATripodi, Dotti JZhuang, JieLago, Cory UStrong, Louise CTalagala, S LalithBalaban, Robert SKang, Ju-GyeongHwang, Paul MN. Engl. J. Med. 368:1027-3222682249Pubmed2012Tumor suppression in the absence of p53-mediated cell-cycle arrest, apoptosis, and senescenceLi, TongyuanKon, NingJiang, LeTan, MinjiaLudwig, ThomasZhao, YingmingBaer, Richard JGu, WeiCell 149:1269-8322864287Pubmed2012PHF20 is an effector protein of p53 double lysine methylation that stabilizes and activates p53Cui, GaofengPark, SungmanBadeaux, Aimee IKim, DonghwaLee, JosephThompson, James RYan, FeiKaneko, SatoshiYuan, ZengqiangBotuyan, Maria VictoriaBedford, Mark TCheng, Jin QMer, GeorgesNat. Struct. Mol. Biol. 19:916-2419696408Pubmed2009p53 improves aerobic exercise capacity and augments skeletal muscle mitochondrial DNA contentPark, Joon-YoungWang, Ping-yuanMatsumoto, TakumiSung, Ho JoongMa, WenzheChoi, Jeong WAnderson, Stasia ALeary, Scot CBalaban, Robert SKang, Ju-GyeongHwang, Paul MCirc. Res. 105:705-12, 11 p following 712TP53 Regulates Transcription of Cell Death GenesThis event has been computationally inferred from an event that has been demonstrated in another species.<p>The inference is based on the homology mapping from PANTHER. Briefly, reactions for which all involved PhysicalEntities (in input, output and catalyst) have a mapped orthologue/paralogue (for complexes at least 75% of components must have a mapping) are inferred to the other species. High level events are also inferred for these events to allow for easier navigation.<p><a href='/electronic_inference_compara.html' target = 'NEW'>More details and caveats of the event inference in Reactome.</a> For details on PANTHER see also: <a href='http://www.pantherdb.org/about.jsp' target='NEW'>http://www.pantherdb.org/about.jsp</a>TP53 Regulates Transcription of Genes Involved in Cytochrome C ReleaseThis event has been computationally inferred from an event that has been demonstrated in another species.<p>The inference is based on the homology mapping from PANTHER. Briefly, reactions for which all involved PhysicalEntities (in input, output and catalyst) have a mapped orthologue/paralogue (for complexes at least 75% of components must have a mapping) are inferred to the other species. High level events are also inferred for these events to allow for easier navigation.<p><a href='/electronic_inference_compara.html' target = 'NEW'>More details and caveats of the event inference in Reactome.</a> For details on PANTHER see also: <a href='http://www.pantherdb.org/about.jsp' target='NEW'>http://www.pantherdb.org/about.jsp</a>LEFT-TO-RIGHT2.7.11ATM phosphorylates ZNF420This event has been computationally inferred from an event that has been demonstrated in another species.<p>The inference is based on the homology mapping from PANTHER. Briefly, reactions for which all involved PhysicalEntities (in input, output and catalyst) have a mapped orthologue/paralogue (for complexes at least 75% of components must have a mapping) are inferred to the other species. High level events are also inferred for these events to allow for easier navigation.<p><a href='/electronic_inference_compara.html' target = 'NEW'>More details and caveats of the event inference in Reactome.</a> For details on PANTHER see also: <a href='http://www.pantherdb.org/about.jsp' target='NEW'>http://www.pantherdb.org/about.jsp</a>ATPAdenosine 5'-triphosphateATP(4-)Reactome DB_ID: 29358nucleoplasmGENE ONTOLOGYGO:0005654Reactome Database ID Release 7529358Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=29358ReactomeR-ALL-293583Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-ALL-29358.3COMPOUNDC00002ZNF384ZNF420A0A1D5P0E4Reactome DB_ID: 10472119UniProt:A0A1D5P0E4ZNF384UniProtA0A1D5P0E41EQUAL688EQUALReactome Database ID Release 7510472119Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10472119ReactomeR-GGA-12475091Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-GGA-1247509.1ADPAdenosine 5'-diphosphateADP(3-)Reactome DB_ID: 113582Reactome Database ID Release 75113582Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=113582ReactomeR-ALL-1135823Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-ALL-113582.3COMPOUNDC00008A0A1D5P0E4phospho-ZNF384p-S68-ZNF420Reactome DB_ID: 1047382468EQUAL1EQUAL688EQUALReactome Database ID Release 7510473824Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10473824ReactomeR-GGA-67990951Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-GGA-6799095.1ACTIVATIONE1C0Q6phospho-p-S1981,Ac-K3016-ATMReactome DB_ID: 10413712UniProt:E1C0Q6UniProtE1C0Q61981EQUAL3016EQUALN6-acetyl-L-lysineMODMOD:000641EQUAL3056EQUALReactome Database ID Release 7510413712Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10413712ReactomeR-GGA-56935271Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-GGA-5693527.1Reactome Database ID Release 7510430180Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10430180Reactome Database ID Release 7510473826Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10473826ReactomeR-GGA-67990971Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-GGA-6799097.1Activated ATM phosphorylates ZNF420 (Apak) at serine residue S68. Phosphorylation at S68 inhibits ZNF420 binding to the first intron of TP53AIP1 (p53AIP1) gene, thus facilitating TP53 (p53)-mediated expression of TP53AIP1 (Yuan et al. 2012). ATM-mediated phosphorylation of ZNF420 also inhibits ZNF420 interaction with TP53 and the consequent TP53 deacetylation (Tian et al. 2009).22334068Pubmed2012Apak competes with p53 for direct binding to intron 1 of p53AIP1 to regulate apoptosisYuan, LinTian, ChunyanWang, HongyeSong, ShanshanLi, DeyangXing, GuichunYin, YuxinHe, FuchuZhang, LingqiangEMBO Rep. 13:363-7019377469Pubmed2009KRAB-type zinc-finger protein Apak specifically regulates p53-dependent apoptosisTian, ChunyanXing, GuichunXie, PingLu, KefengNie, JingWang, JianLi, LGao, MeiZhang, LingqiangHe, FuchuNat. Cell Biol. 11:580-91LEFT-TO-RIGHTSTEAP3 binds BNIP3LThis event has been computationally inferred from an event that has been demonstrated in another species.<p>The inference is based on the homology mapping from PANTHER. Briefly, reactions for which all involved PhysicalEntities (in input, output and catalyst) have a mapped orthologue/paralogue (for complexes at least 75% of components must have a mapping) are inferred to the other species. High level events are also inferred for these events to allow for easier navigation.<p><a href='/electronic_inference_compara.html' target = 'NEW'>More details and caveats of the event inference in Reactome.</a> For details on PANTHER see also: <a href='http://www.pantherdb.org/about.jsp' target='NEW'>http://www.pantherdb.org/about.jsp</a>STEAP3STEAP3A0A1D5PJT4Reactome DB_ID: 10440847endosome membraneGENE ONTOLOGYGO:0010008UniProt:A0A1D5PJT4STEAP3UniProtA0A1D5PJT41EQUAL488EQUALReactome Database ID Release 7510440847Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10440847ReactomeR-GGA-9178611Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-GGA-917861.1BNIP3LBNIP3LA0A3Q2UGF2Reactome DB_ID: 10474705mitochondrial outer membraneGENE ONTOLOGYGO:0005741UniProt:A0A3Q2UGF2BNIP3LUniProtA0A3Q2UGF21EQUAL219EQUALReactome Database ID Release 7510474705Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10474705ReactomeR-GGA-67980011Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-GGA-6798001.1STEAP3:BNIP3LReactome DB_ID: 1047470711Reactome Database ID Release 7510474707Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10474707ReactomeR-GGA-68011981Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-GGA-6801198.1Reactome Database ID Release 7510474709Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10474709ReactomeR-GGA-68011951Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-GGA-6801195.1STEAP3 (TSAP6) forms a complex with a pro-apoptotic protein BNIP3L (NIX) and cooperates with BNIP3L in promoting apoptosis, but the exact mechanism is not known (Passer et al. 2003).<p>While STEAP3 localizes to endosome membranes, BNIP3L localizes to the outer mitochondrial membrane. BNIP3L has recently been implicated in the relocalization of endo-lysosomes to inner mitochondrial compartments, which can play a role in endo-lysosomal processing of mitochondria (Hamacher-Brady et al. 2014).25080938Pubmed2014Intramitochondrial recruitment of endolysosomes mediates Smac degradation and constitutes a novel intrinsic apoptosis antagonizing function of XIAP E3 ligaseHamacher-Brady, AChoe, S CKrijnse-Locker, JBrady, N RCell Death Differ. 21:1862-7612606722Pubmed2003The p53-inducible TSAP6 gene product regulates apoptosis and the cell cycle and interacts with Nix and the Myt1 kinasePasser, Brent JNancy-Portebois, VanessaAmzallag, NathaliePrieur, SylvieCans, ChristopheRoborel de Climens, AudeFiucci, GiusyBouvard, VeroniqueTuynder, MarcelSusini, LaurentMorchoisne, StéphanieCrible, VirginieLespagnol, AlexandraDausset, JeanOren, MAmson, RobertTelerman, AdamProc. Natl. Acad. Sci. U.S.A. 100:2284-9Reactome Database ID Release 7510490376Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10490376ReactomeR-GGA-68032041Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-GGA-6803204.1Apoptotic transcriptional targets of TP53 include genes that regulate the permeability of the mitochondrial membrane and/or cytochrome C release, such as BAX, BID, PMAIP1 (NOXA), BBC3 (PUMA) and probably BNIP3L, AIFM2, STEAP3, TRIAP1 and TP53AIP1 (Miyashita and Reed 1995, Oda et al. 2000, Samuels-Lev et al. 2001, Nakano and Vousden 2001, Sax et al. 2002, Passer et al. 2003, Bergamaschi et al. 2004, Li et al. 2004, Fei et al. 2004, Wu et al. 2004, Park and Nakamura 2005, Patel et al. 2008, Wang et al. 2012, Wilson et al. 2013), thus promoting the activation of the apoptotic pathway.<p>Transcriptional activation of TP53AIP1 requires phosphorylation of TP53 at serine residue S46 (Oda et al. 2000, Taira et al. 2007). Phosphorylation of TP53 at S46 is regulated by another TP53 pro-apoptotic target, TP53INP1 (Okamura et al. 2001, Tomasini et al. 2003).14729977Pubmed2004ASPP1 and ASPP2: common activators of p53 family membersBergamaschi, DanieleSamuels, YJin, BDuraisingham, SaiCrook, TimLu, XinMol. Cell. Biol. 24:1341-5015735003Pubmed2005p53CSV, a novel p53-inducible gene involved in the p53-dependent cell-survival pathwayPark, Woong-RyeonNakamura, YusukeCancer Res. 65:1197-20612851404Pubmed2003TP53INP1s and homeodomain-interacting protein kinase-2 (HIPK2) are partners in regulating p53 activityTomasini, RichardSamir, Amina AziziCarrier, AliceIsnardon, DanielCecchinelli, BarbaraSoddu, SilviaMalissen, BernardDagorn, Jean-CharlesIovanna, Juan LDusetti, Nelson JJ. Biol. Chem. 278:37722-918676979Pubmed2008Molecular interactions of ASPP1 and ASPP2 with the p53 protein family and the apoptotic promoters PUMA and BaxPatel, SeemaGeorge, RogerAutore, FlaviaFraternali, FrancaLadbury, JENikolova, Penka VNucleic Acids Res. 36:5139-5110807576Pubmed2000Noxa, a BH3-only member of the Bcl-2 family and candidate mediator of p53-induced apoptosisOda, EOhki, RMurasawa, HNemoto, JShibue, TYamashita, TTokino, TTaniguchi, TTanaka, NScience 288:1053-812402042Pubmed2002BID regulation by p53 contributes to chemosensitivitySax, Joanna KFei, PeiwenMurphy, Maureen EBernhard, EricKorsmeyer, Stanley JEl-Deiry, Wafik SNat. Cell Biol. 4:842-911511362Pubmed2001p53DINP1, a p53-inducible gene, regulates p53-dependent apoptosisOkamura, SArakawa, HTanaka, TNakanishi, HNg, C CTaya, YMonden, MNakamura, YMol. Cell 8:85-9411684014Pubmed2001ASPP proteins specifically stimulate the apoptotic function of p53Samuels-Lev, YO'Connor, D JBergamaschi, DTrigiante, GHsieh, J KZhong, SCampargue, INaumovski, LCrook, TLu, XMol. Cell 8:781-9422766503Pubmed2012iASPPsv antagonizes apoptosis induced by chemotherapeutic agents in MCF-7 cells and mouse thymocytesWang, LinXing, HaiyanTian, ZhengPeng, LeiwenLi, YTang, KejingRao, QingWang, MinWang, JianxiangBiochem. Biophys. Res. Commun. 424:414-2015273740Pubmed2004AMID is a p53-inducible gene downregulated in tumorsWu, MinXu, Liang-GuoSu, TianTian, YangZhai, ZhongheShu, Hong-BingOncogene 23:6815-915607964Pubmed2004Bnip3L is induced by p53 under hypoxia, and its knockdown promotes tumor growthFei, PeiwenWang, WengeKim, Seok-hyunWang, ShulinBurns, Timothy FSax, Joanna KBuzzai, MonicaDicker, David TMcKenna, W GilliesBernhard, Eric JEl-Deiry, Wafik SCancer Cell 6:597-60923365256Pubmed2013ASPP1/2 regulate p53-dependent death of retinal ganglion cells through PUMA and Fas/CD95 activation in vivoWilson, Ariel MMorquette, BarbaraAbdouh, MohamedUnsain, NicolásBarker, Philip AFeinstein, ElenaBernier, GilbertDi Polo, AdrianaJ. Neurosci. 33:2205-1611463392Pubmed2001PUMA, a novel proapoptotic gene, is induced by p53Nakano, KVousden, KHMol Cell 7:683-947834749Pubmed1995Tumor suppressor p53 is a direct transcriptional activator of the human bax geneMiyashita, TReed, J CCell 80:293-915126337Pubmed2004Apoptotic signaling pathways induced by nitric oxide in human lymphoblastoid cells expressing wild-type or mutant p53Li, CQRobles, AIHanigan, CLHofseth, LJTrudel, LJHarris, CCWogan, GNCancer Res 64:3022-9TP53 regulates transcription of several additional cell death genes whose specific roles in p53-dependent apoptosis remain uncertainThis event has been computationally inferred from an event that has been demonstrated in another species.<p>The inference is based on the homology mapping from PANTHER. Briefly, reactions for which all involved PhysicalEntities (in input, output and catalyst) have a mapped orthologue/paralogue (for complexes at least 75% of components must have a mapping) are inferred to the other species. High level events are also inferred for these events to allow for easier navigation.<p><a href='/electronic_inference_compara.html' target = 'NEW'>More details and caveats of the event inference in Reactome.</a> For details on PANTHER see also: <a href='http://www.pantherdb.org/about.jsp' target='NEW'>http://www.pantherdb.org/about.jsp</a>LEFT-TO-RIGHTTP53I3 dimerizesThis event has been computationally inferred from an event that has been demonstrated in another species.<p>The inference is based on the homology mapping from PANTHER. Briefly, reactions for which all involved PhysicalEntities (in input, output and catalyst) have a mapped orthologue/paralogue (for complexes at least 75% of components must have a mapping) are inferred to the other species. High level events are also inferred for these events to allow for easier navigation.<p><a href='/electronic_inference_compara.html' target = 'NEW'>More details and caveats of the event inference in Reactome.</a> For details on PANTHER see also: <a href='http://www.pantherdb.org/about.jsp' target='NEW'>http://www.pantherdb.org/about.jsp</a>TP53I3TP53I3F1NUE4Reactome DB_ID: 10474096UniProt:F1NUE4TP53I3UniProtF1NUE41EQUAL332EQUALReactome Database ID Release 7510474096Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10474096ReactomeR-GGA-67994601Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-GGA-6799460.12TP53I3 DimerReactome DB_ID: 104740982Reactome Database ID Release 7510474098Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10474098ReactomeR-GGA-67994481Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-GGA-6799448.1Reactome Database ID Release 7510474100Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10474100ReactomeR-GGA-67994661Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-GGA-6799466.1TP53I3 (PIG3) forms a homodimer. The dimer interface is formed by two beta strands and an alpha helix of the cofactor-binding domain. Beta strands of the two monomeric subunits are bonded through anti-parallel hydrogen bonds (Porte et al. 2009).19349281Pubmed2009Three-dimensional structure and enzymatic function of proapoptotic human p53-inducible quinone oxidoreductase PIG3Porté, SergioValencia, EvaYakovtseva, Evgenia ABorràs, EmmaShafqat, NaeemDebreczeny, Judit EPike, Ashley C WOppermann, UFarrés, JaumeFita, IgnacioParés, XavierJ. Biol. Chem. 284:17194-205LEFT-TO-RIGHT1.6.5.5TP53I3 oxidoreductase generates unstable semiquinonesThis event has been computationally inferred from an event that has been demonstrated in another species.<p>The inference is based on the homology mapping from PANTHER. Briefly, reactions for which all involved PhysicalEntities (in input, output and catalyst) have a mapped orthologue/paralogue (for complexes at least 75% of components must have a mapping) are inferred to the other species. High level events are also inferred for these events to allow for easier navigation.<p><a href='/electronic_inference_compara.html' target = 'NEW'>More details and caveats of the event inference in Reactome.</a> For details on PANTHER see also: <a href='http://www.pantherdb.org/about.jsp' target='NEW'>http://www.pantherdb.org/about.jsp</a>1,2-NaphthoquinoneReactome DB_ID: 67997251,2-Naphthoquinone [ChEBI:34055]1,2-Naphthoquinone1,2-NaphthalenedioneChEBICHEBI:34055Reactome Database ID Release 756799725Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=6799725ReactomeR-ALL-67997252Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-ALL-6799725.22semiquinonephys-ent-participant42974Reactome DB_ID: 6799726semiquinone [ChEBI:15817]semiquinoneSemidioneSemiquinone radicalsemiquinonesChEBICHEBI:15817Reactome Database ID Release 756799726Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=6799726ReactomeR-ALL-67997262Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-ALL-6799726.22ACTIVATIONGENE ONTOLOGYGO:0003960Reactome Database ID Release 7510474152Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10474152Reactome Database ID Release 7510474154Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10474154ReactomeR-GGA-67997221Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-GGA-6799722.1TP53I3 (PIG3) possesses a NADPH quinone reductase activity, with 1,2-naphthoquinone being its preferred substrate. TP53I3 reduces 1,2-naphthoquinone to a highly unstable semiquinone free radical. Semiquinone reacts with oxygen yielding a quinone and superoxide aninon. Reactive oxygen species (ROS) produced as a result of TP53I3 activity contribute to apoptosis (Porte et al. 2009).Reactome Database ID Release 7510490380Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10490380ReactomeR-GGA-68032051Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-GGA-6803205.1The exact mechanisms of action of several other pro-apoptotic TP53 (p53) targets, such as TP53I3 (PIG3), RABGGTA, BCL2L14, BCL6, NDRG1 and PERP, remain uncertain (Attardi et al. 2000, Guo et al. 2001, Samuels-Lev et al. 2001, Contente et al. 2002, Ihrie et al. 2003, Bergamaschi et al. 2004, Stein et al. 2004, Phan and Dalla-Favera 2004, Jen and Cheung 2005, Margalit et al. 2006, Zhang et al. 2007, Saito et al. 2009, Davies et al. 2009, Giam et al. 2012).16249378Pubmed2006BCL6 is regulated by p53 through a response element frequently disrupted in B-cell non-Hodgkin lymphomaMargalit, OferAmram, HilaAmariglio, NinetteSimon, Amos JShaklai, SigalGranot, GalitMinsky, NeriShimoni, AvichaiHarmelin, AlonGivol, DavidShohat, MordechaiOren, MRechavi, GideonBlood 107:1599-60715577913Pubmed2004The BCL6 proto-oncogene suppresses p53 expression in germinal-centre B cellsPhan, Ryan TDalla-Favera, RiccardoNature 432:635-911054413Pubmed2001Bcl-G, a novel pro-apoptotic member of the Bcl-2 familyGuo, BGodzik, AReed, J CJ. Biol. Chem. 276:2780-519040420Pubmed2009P53 apoptosis mediator PERP: localization, function and caspase activation in uveal melanomaDavies, LyndsayGray, DonnaSpiller, DaveWhite, Mike R HDamato, BertilGrierson, IanParaoan, LuminitaJ. Cell. Mol. Med. 13:1995-200717442733Pubmed2007p53-dependent NDRG1 expression induces inhibition of intestinal epithelial cell proliferation but not apoptosis after polyamine depletionZhang, Ai-HongRao, Jaladanki NZou, TongtongLiu, LanMarasa, Bernard SXiao, LanChen, JieTurner, Douglas JWang, Jian-YingAm. J. Physiol., Cell Physiol. 293:C379-8911919562Pubmed2002A polymorphic microsatellite that mediates induction of PIG3 by p53Contente, AnaDittmer, AlexandraKoch, Manuela CRoth, JudithDobbelstein, MatthiasNat. Genet. 30:315-2016140933Pubmed2005Identification of novel p53 target genes in ionizing radiation responseJen, Kuang-YuCheung, Vivian GCancer Res. 65:7666-7323059823Pubmed2012Bcl-2 family member Bcl-G is not a proapoptotic proteinGiam, MOkamoto, TMintern, J DStrasser, ABouillet, PCell Death Dis 3:e40415377670Pubmed2004NDRG1 is necessary for p53-dependent apoptosisStein, SusanneThomas, Emily KHerzog, BirgerWestfall, Matthew DRocheleau, Jonathan VJackson, Roger SWang, MaiLiang, PengJ. Biol. Chem. 279:48930-4019549844Pubmed2009BCL6 suppression of BCL2 via Miz1 and its disruption in diffuse large B cell lymphomaSaito, MasumichiNovak, UrbanPiovan, ErichBasso, KSumazin, PavelSchneider, ChristofCrespo, MartaShen, QiongBhagat, GCalifano, AChadburn, AmyPasqualucci, LauraDalla-Favera, RiccardoProc. Natl. Acad. Sci. U.S.A. 106:11294-914614825Pubmed2003Perp is a mediator of p53-dependent apoptosis in diverse cell typesIhrie, Rebecca AReczek, ElizabethHorner, Jennifer SKhachatrian, LeiliSage, JJacks, TylerAttardi, Laura DCurr. Biol. 13:1985-9010733530Pubmed2000PERP, an apoptosis-associated target of p53, is a novel member of the PMP-22/gas3 familyAttardi, L DReczek, E ECosmas, CDemicco, E GMcCurrach, M ELowe, S WJacks, TGenes Dev. 14:704-18Reactome Database ID Release 7510490378Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10490378ReactomeR-GGA-56330081Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-GGA-5633008.1GENE ONTOLOGYGO:0042981The tumor suppressor TP53 (p53) exerts its tumor suppressive role in part by regulating transcription of a number of genes involved in cell death, mainly apoptotic cell death. The majority of apoptotic genes that are transcriptional targets of TP53 promote apoptosis, but there are also several TP53 target genes that inhibit apoptosis, providing cells with an opportunity to attempt to repair the damage and/or recover from stress. <br>Pro-apoptotic transcriptional targets of TP53 involve TRAIL death receptors TNFRSF10A (DR4), TNFRSF10B (DR5), TNFRSF10C (DcR1) and TNFRSF10D (DcR2), as well as the FASL/CD95L death receptor FAS (CD95). TRAIL receptors and FAS induce pro-apoptotic signaling in response to external stimuli via extrinsic apoptosis pathway (Wu et al. 1997, Takimoto et al. 2000, Guan et al. 2001, Liu et al. 2004, Ruiz de Almodovar et al. 2004, Liu et al. 2005, Schilling et al. 2009, Wilson et al. 2013). IGFBP3 is a transcriptional target of TP53 that may serve as a ligand for a novel death receptor TMEM219 (Buckbinder et al. 1995, Ingermann et al. 2010).<p>TP53 regulates expression of a number of genes involved in the intrinsic apoptosis pathway, triggered by the cellular stress. Some of TP53 targets, such as BAX, BID, PMAIP1 (NOXA), BBC3 (PUMA) and probably BNIP3L, AIFM2, STEAP3, TRIAP1 and TP53AIP1, regulate the permeability of the mitochondrial membrane and/or cytochrome C release (Miyashita and Reed 1995, Oda et al. 2000, Samuels-Lev et al. 2001, Nakano and Vousden 2001, Sax et al. 2002, Passer et al. 2003, Bergamaschi et al. 2004, Li et al. 2004, Fei et al. 2004, Wu et al. 2004, Park and Nakamura 2005, Patel et al. 2008, Wang et al. 2012, Wilson et al. 2013). Other pro-apoptotic genes, either involved in the intrinsic apoptosis pathway, extrinsic apoptosis pathway or pyroptosis (inflammation-related cell death), which are transcriptionally regulated by TP53 are cytosolic caspase activators, such as APAF1, PIDD1, and NLRC4, and caspases themselves, such as CASP1, CASP6 and CASP10 (Lin et al. 2000, Robles et al. 2001, Gupta et al. 2001, MacLachlan and El-Deiry 2002, Rikhof et al. 2003, Sadasivam et al. 2005, Brough and Rothwell 2007).<p>It is uncertain how exactly some of the pro-apoptotic TP53 targets, such as TP53I3 (PIG3), RABGGTA, BCL2L14, BCL6, NDRG1 and PERP contribute to apoptosis (Attardi et al. 2000, Guo et al. 2001, Samuels-Lev et al. 2001, Contente et al. 2002, Ihrie et al. 2003, Bergamaschi et al. 2004, Stein et al. 2004, Phan and Dalla-Favera 2004, Jen and Cheung 2005, Margalit et al. 2006, Zhang et al. 2007, Saito et al. 2009, Davies et al. 2009, Giam et al. 2012).<p>TP53 is stabilized in response to cellular stress by phosphorylation on at least serine residues S15 and S20. Since TP53 stabilization precedes the activation of cell death genes, the TP53 tetramer phosphorylated at S15 and S20 is shown as a regulator of pro-apoptotic/pro-cell death genes. Some pro-apoptotic TP53 target genes, such as TP53AIP1, require additional phosphorylation of TP53 at serine residue S46 (Oda et al. 2000, Taira et al. 2007). Phosphorylation of TP53 at S46 is regulated by another TP53 pro-apoptotic target, TP53INP1 (Okamura et al. 2001, Tomasini et al. 2003). Additional post-translational modifications of TP53 may be involved in transcriptional regulation of genes presented in this pathway and this information will be included as evidence becomes available.<p>Activation of some pro-apoptotic TP53 targets, such as BAX, FAS, BBC3 (PUMA) and TP53I3 (PIG3) requires the presence of the complex of TP53 and an ASPP protein, either PPP1R13B (ASPP1) or TP53BP2 (ASPP2) (Samuels-Lev et al. 2001, Bergamaschi et al. 2004, Patel et al. 2008, Wilson et al. 2013), indicating how the interaction with specific co-factors modulates the cellular response/outcome.<p>TP53 family members TP63 and or TP73 can also activate some of the pro-apoptotic TP53 targets, such as FAS, BAX, BBC3 (PUMA), TP53I3 (PIG3), CASP1 and PERP (Bergamaschi et al. 2004, Jain et al. 2005, Ihrie et al. 2005, Patel et al. 2008, Schilling et al. 2009, Celardo et al. 2013).<p> <br>For a review of the role of TP53 in apoptosis and pro-apoptotic transcriptional targets of TP53, please refer to Riley et al. 2008, Murray-Zmijewski et al. 2008, Bieging et al. 2014, Kruiswijk et al. 2015.23703390Pubmed2013Caspase-1 is a novel target of p63 in tumor suppressionCelardo, IGrespi, FAntonov, ABernassola, FGarabadgiu, A VMelino, GAmelio, ICell Death Dis 4:e64514623878Pubmed2004Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) decoy receptor TRAIL-R3 is up-regulated by p53 in breast tumor cells through a mechanism involving an intronic p53-binding siteRuiz de Almodóvar, CarmenRuiz-Ruiz, CarmenRodríguez, AntonioOrtiz-Ferrón, GustavoRedondo, Juan MiguelLópez-Rivas, AbelardoJ. Biol. Chem. 279:4093-10116230375Pubmed2005Decoy receptor 2 (DcR2) is a p53 target gene and regulates chemosensitivityLiu, XiangguoYue, PingKhuri, Fadlo RSun, Shi-YongCancer Res. 65:9169-7519615968Pubmed2009Active transcription of the human FAS/CD95/TNFRSF6 gene involves the p53 familySchilling, TobiasSchleithoff, Elisa SchulzeKairat, AstridMelino, GerryStremmel, WolfgangOren, MKrammer, Peter HMüller, MartinaBiochem. Biophys. Res. Commun. 387:399-4049326928Pubmed1997KILLER/DR5 is a DNA damage-inducible p53-regulated death receptor geneWu, G SBurns, T FMcDonald, E RJiang, WMeng, RKrantz, I DKao, GGan, D DZhou, J YMuschel, RHamilton, S RSpinner, N BMarkowitz, SWu, Gel-Deiry, WSNat. Genet. 17:141-317349958Pubmed2007DYRK2 is targeted to the nucleus and controls p53 via Ser46 phosphorylation in the apoptotic response to DNA damageTaira, NaoeNihira, KeishiYamaguchi, TomokoMiki, YoshioYoshida, KiyotsuguMol. Cell 25:725-3820353938Pubmed2010Identification of a novel cell death receptor mediating IGFBP-3-induced anti-tumor effects in breast and prostate cancerIngermann, Angela RYang, Yong-FengHan, JinfengMikami, AkiGarza, Amanda EMohanraj, LathikaFan, LingboIdowu, MichaelWare, Joy LKim, Ho-SeongLee, Dae-YeolOh, YoungmanJ. Biol. Chem. 285:30233-4615289308Pubmed2004p53 upregulates death receptor 4 expression through an intronic p53 binding siteLiu, XiangguoYue, PingKhuri, Fadlo RSun, Shi-YongCancer Res. 64:5078-8314688482Pubmed2003Caspase 10 levels are increased following DNA damage in a p53-dependent mannerRikhof, BartCorn, Paul GEl-Deiry, Wafik SCancer Biol. Ther. 2:707-1211382926Pubmed2001Evidence that the death receptor DR4 is a DNA damage-inducible, p53-regulated geneGuan, BYue, PClayman, G LSun, S YJ. Cell. Physiol. 188:98-1057566179Pubmed1995Induction of the growth inhibitor IGF-binding protein 3 by p53Buckbinder, LTalbott, RVelasco-Miguel, STakenaka, IFaha, BSeizinger, B RKley, NNature 377:646-918431400Pubmed2008Transcriptional control of human p53-regulated genesRiley, ToddSontag, EduardoChen, PatriciaLevine, ArnoldNat. Rev. Mol. Cell Biol. 9:402-1224739573Pubmed2014Unravelling mechanisms of p53-mediated tumour suppressionBieging, Kathryn TMello, Stephano SpanoAttardi, Laura DNat. Rev. Cancer 14:359-7015580302Pubmed2005Caspase-1 activator Ipaf is a p53-inducible gene involved in apoptosisSadasivam, SGupta, SRadha, VegesnaBatta, KiranKundu, Tapas KSwarup, GhanshyamOncogene 24:627-3616135520Pubmed2005Role of p73 in regulating human caspase-1 gene transcription induced by interferon-{gamma} and cisplatinJain, NishantGupta, SSudhakar, ChRadha, VegesnaSwarup, GhanshyamJ. Biol. Chem. 280:36664-7310973264Pubmed2000Pidd, a new death-domain-containing protein, is induced by p53 and promotes apoptosisLin, YMa, WBenchimol, SNat. Genet. 26:122-711278253Pubmed2001Direct transcriptional activation of human caspase-1 by tumor suppressor p53Gupta, SRadha, VFurukawa, YSwarup, GJ. Biol. Chem. 276:10585-811559530Pubmed2001APAF-1 is a transcriptional target of p53 in DNA damage-induced apoptosisRobles, A IBemmels, N AForaker, A BHarris, C CCancer Res. 61:6660-415797384Pubmed2005Perp is a p63-regulated gene essential for epithelial integrityIhrie, Rebecca AMarques, Michelle RNguyen, Bichchau THorner, Jennifer SPapazoglu, CristianBronson, Roderick TMills, Alea AAttardi, Laura DCell 120:843-5618719709Pubmed2008A complex barcode underlies the heterogeneous response of p53 to stressMurray-Zmijewski, FionaSlee, Elizabeth ALu, XinNat. Rev. Mol. Cell Biol. 9:702-1210777207Pubmed2000Wild-type p53 transactivates the KILLER/DR5 gene through an intronic sequence-specific DNA-binding siteTakimoto, Rel-Deiry, WSOncogene 19:1735-4317284521Pubmed2007Caspase-1-dependent processing of pro-interleukin-1beta is cytosolic and precedes cell deathBrough, DRothwell, NJJ Cell Sci 120:772-8112089322Pubmed2002Apoptotic threshold is lowered by p53 transactivation of caspase-6MacLachlan, Timothy KEl-Deiry, Wafik SProc. Natl. Acad. Sci. U.S.A. 99:9492-726122615Pubmed2015p53 in survival, death and metabolic health: a lifeguard with a licence to killKruiswijk, FloreLabuschagne, Christiaan FVousden, Karen HNat. Rev. Mol. Cell Biol. 16:393-405TP53 Regulates Transcription of Cell Cycle GenesThis event has been computationally inferred from an event that has been demonstrated in another species.<p>The inference is based on the homology mapping from PANTHER. Briefly, reactions for which all involved PhysicalEntities (in input, output and catalyst) have a mapped orthologue/paralogue (for complexes at least 75% of components must have a mapping) are inferred to the other species. High level events are also inferred for these events to allow for easier navigation.<p><a href='/electronic_inference_compara.html' target = 'NEW'>More details and caveats of the event inference in Reactome.</a> For details on PANTHER see also: <a href='http://www.pantherdb.org/about.jsp' target='NEW'>http://www.pantherdb.org/about.jsp</a>TP53 Regulates Transcription of Genes Involved in G1 Cell Cycle ArrestThis event has been computationally inferred from an event that has been demonstrated in another species.<p>The inference is based on the homology mapping from PANTHER. Briefly, reactions for which all involved PhysicalEntities (in input, output and catalyst) have a mapped orthologue/paralogue (for complexes at least 75% of components must have a mapping) are inferred to the other species. High level events are also inferred for these events to allow for easier navigation.<p><a href='/electronic_inference_compara.html' target = 'NEW'>More details and caveats of the event inference in Reactome.</a> For details on PANTHER see also: <a href='http://www.pantherdb.org/about.jsp' target='NEW'>http://www.pantherdb.org/about.jsp</a>LEFT-TO-RIGHTInactivation of Cyclin A:Cdk2 complexes by p27/p21This event has been computationally inferred from an event that has been demonstrated in another species.<p>The inference is based on the homology mapping from PANTHER. Briefly, reactions for which all involved PhysicalEntities (in input, output and catalyst) have a mapped orthologue/paralogue (for complexes at least 75% of components must have a mapping) are inferred to the other species. High level events are also inferred for these events to allow for easier navigation.<p><a href='/electronic_inference_compara.html' target = 'NEW'>More details and caveats of the event inference in Reactome.</a> For details on PANTHER see also: <a href='http://www.pantherdb.org/about.jsp' target='NEW'>http://www.pantherdb.org/about.jsp</a>CCNA:CDK2Reactome DB_ID: 10423040Converted from EntitySet in ReactomeCCNACyclin AReactome DB_ID: 10413426CCNA1F1P4N0Reactome DB_ID: 10413420UniProt:F1P4N0UniProtF1P4N01EQUAL465EQUALReactome Database ID Release 7510413420Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10413420ReactomeR-GGA-688911Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-GGA-68891.1CCNA2CCNA2F1NJI2Reactome DB_ID: 10413424UniProt:F1NJI2CCNA2UniProtF1NJI21EQUAL432EQUALReactome Database ID Release 7510413424Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10413424ReactomeR-GGA-689051Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-GGA-68905.1Reactome Database ID Release 7510413426Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10413426ReactomeR-GGA-752021Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-GGA-75202.11CDK2CDK2A2IAR9Reactome DB_ID: 10413369UniProt:A2IAR9CDK2UniProtA2IAR91EQUAL298EQUALReactome Database ID Release 7510413369Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10413369ReactomeR-GGA-683651Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-GGA-68365.11Reactome Database ID Release 7510423040Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10423040ReactomeR-GGA-1416081Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-GGA-141608.1Converted from EntitySet in Reactomep21,p27CDKN1A,CDKN1BReactome DB_ID: 10424182CDKN1ACDKN1AA0A3Q2UBS2Reactome DB_ID: 10424180UniProt:A0A3Q2UBS2CDKN1AUniProtA0A3Q2UBS22EQUAL164EQUALReactome Database ID Release 7510424180Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10424180ReactomeR-GGA-1825851Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-GGA-182585.1CDKN1BCDKN1BQ8JIV2Reactome DB_ID: 10424174UniProt:Q8JIV2CDKN1BUniProtQ8JIV21EQUAL198EQUALReactome Database ID Release 7510424174Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10424174ReactomeR-GGA-1825631Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-GGA-182563.1Reactome Database ID Release 7510424182Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10424182ReactomeR-GGA-1825581Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-GGA-182558.1Cyclin A:Cdk2:p21/p27 complexReactome DB_ID: 1042425011Reactome Database ID Release 7510424250Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10424250ReactomeR-GGA-1879261Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-GGA-187926.1ACTIVATIONGENE ONTOLOGYGO:0004861Reactome Database ID Release 7510424256Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10424256Reactome Database ID Release 7510424258Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10424258ReactomeR-GGA-1879341Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-GGA-187934.1During G1, the activity of cyclin-dependent kinases (CDKs) is controlled by the CDK inhibitors (CKIs) CDKN1A (p21) and CDKN1B (p27), thereby preventing premature entry into S phase (Guardavaccaro and Pagano, 2006). 8242751Pubmed1993The p21 Cdk-interacting protein Cip1 is a potent inhibitor of G1 cyclin-dependent kinases.Harper, JWAdami, GRWei, NKeyomarsi, KElledge, SJCell 75:805-167624798Pubmed1995Role of the ubiquitin-proteasome pathway in regulating abundance of the cyclin-dependent kinase inhibitor p27Pagano, MicheleTam, SWTheodoras, AMBeer-Romero, PDel Sal, GChau, VYew, PRDraetta, GFRolfe, MScience 269:682-510323868Pubmed1999Ubiquitination of p27 is regulated by Cdk-dependent phosphorylation and trimeric complex formationMontagnoli, AFiore, FEytan, ECarrano, ACDraetta, GFHershko, APagano, MicheleGenes Dev 13:1181-9LEFT-TO-RIGHTE2F7 forms homodimersThis event has been computationally inferred from an event that has been demonstrated in another species.<p>The inference is based on the homology mapping from PANTHER. Briefly, reactions for which all involved PhysicalEntities (in input, output and catalyst) have a mapped orthologue/paralogue (for complexes at least 75% of components must have a mapping) are inferred to the other species. High level events are also inferred for these events to allow for easier navigation.<p><a href='/electronic_inference_compara.html' target = 'NEW'>More details and caveats of the event inference in Reactome.</a> For details on PANTHER see also: <a href='http://www.pantherdb.org/about.jsp' target='NEW'>http://www.pantherdb.org/about.jsp</a>E2F7A0A1D5P6T6Reactome DB_ID: 10484156UniProt:A0A1D5P6T6UniProtA0A1D5P6T61EQUAL911EQUALReactome Database ID Release 7510484156Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10484156ReactomeR-GGA-67983051Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-GGA-6798305.12E2F7 homodimerReactome DB_ID: 104841582Reactome Database ID Release 7510484158Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10484158ReactomeR-GGA-89530001Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-GGA-8953000.1Reactome Database ID Release 7510484160Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10484160ReactomeR-GGA-89529961Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-GGA-8952996.1E2F7 forms homodimers (Di Stefano et al. 2003, Logan et al. 2004). While E2F7 also forms heterodimers with E2F8, co-immunoprecipitation experiments suggest that E2F7 has higher affinity for itself than for E2F8 (Li et al. 2008)18194653Pubmed2008Synergistic function of E2F7 and E2F8 is essential for cell survival and embryonic developmentLi, JingRan, CongLi, EdwardGordon, FayeComstock, GrantSiddiqui, HasanCleghorn, WhitneyChen, Hui-ZiKornacker, KarlLiu, Chang-gongPandit, Shusil KKhanizadeh, MehrbodWeinstein, MichaelLeone, Gustavode Bruin, AlainDev. Cell 14:62-7514633988Pubmed2003E2F7, a novel E2F featuring DP-independent repression of a subset of E2F-regulated genesDi Stefano, LuisaJensen, Michael RugaardHelin, KristianEMBO J. 22:6289-9815133492Pubmed2004E2F-7: a distinctive E2F family member with an unusual organization of DNA-binding domainsLogan, NicolaDelavaine, LaurentGraham, AnneReilly, CarmelWilson, JonBrummelkamp, Thijn RHijmans, E MarielleBernards, RLa Thangue, Nicholas BOncogene 23:5138-50LEFT-TO-RIGHTE2F7 binds E2F8This event has been computationally inferred from an event that has been demonstrated in another species.<p>The inference is based on the homology mapping from PANTHER. Briefly, reactions for which all involved PhysicalEntities (in input, output and catalyst) have a mapped orthologue/paralogue (for complexes at least 75% of components must have a mapping) are inferred to the other species. High level events are also inferred for these events to allow for easier navigation.<p><a href='/electronic_inference_compara.html' target = 'NEW'>More details and caveats of the event inference in Reactome.</a> For details on PANTHER see also: <a href='http://www.pantherdb.org/about.jsp' target='NEW'>http://www.pantherdb.org/about.jsp</a>E2F8E2F8A0A1D5PQF7Reactome DB_ID: 10484164UniProt:A0A1D5PQF7E2F8UniProtA0A1D5PQF71EQUAL867EQUALReactome Database ID Release 7510484164Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10484164ReactomeR-GGA-89529901Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-GGA-8952990.1E2F7:E2F8Reactome DB_ID: 1048416611Reactome Database ID Release 7510484166Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10484166ReactomeR-GGA-89530171Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-GGA-8953017.1Reactome Database ID Release 7510484168Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10484168ReactomeR-GGA-89530131Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-GGA-8953013.1E2F7 forms heterodimers with E2F8 (Li et al. 2008, Zalmas et al. 2008).18202719Pubmed2008DNA-damage response control of E2F7 and E2F8Zalmas, Lykourgos-PanagiotisZhao, XiujieGraham, Anne LFisher, RebeccaReilly, CarmelCoutts, Amanda SLa Thangue, Nicholas BEMBO Rep. 9:252-9LEFT-TO-RIGHTE2F8 forms homodimersThis event has been computationally inferred from an event that has been demonstrated in another species.<p>The inference is based on the homology mapping from PANTHER. Briefly, reactions for which all involved PhysicalEntities (in input, output and catalyst) have a mapped orthologue/paralogue (for complexes at least 75% of components must have a mapping) are inferred to the other species. High level events are also inferred for these events to allow for easier navigation.<p><a href='/electronic_inference_compara.html' target = 'NEW'>More details and caveats of the event inference in Reactome.</a> For details on PANTHER see also: <a href='http://www.pantherdb.org/about.jsp' target='NEW'>http://www.pantherdb.org/about.jsp</a>2E2F8 homodimerReactome DB_ID: 104841702Reactome Database ID Release 7510484170Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10484170ReactomeR-GGA-89530351Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-GGA-8953035.1Reactome Database ID Release 7510484172Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10484172ReactomeR-GGA-89530371Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-GGA-8953037.1E2F8 forms homodimers (Maiti et al. 2005, Li et al. 2008). E2F8 also forms heterodimers with E2F7 and co-immunoprecipitation experiments suggest that E2F8 has higher affinity for E2F7 than for itself (Zalmas et al. 2008, Li et al. 2008).15722552Pubmed2005Cloning and characterization of mouse E2F8, a novel mammalian E2F family member capable of blocking cellular proliferationMaiti, BaidehiLi, Jingde Bruin, AlainGordon, FayeTimmers, CynthiaOpavsky, RenePatil, KaustubhaTuttle, JohnCleghorn, WhitneyLeone, GustavoJ. Biol. Chem. 280:18211-20Reactome Database ID Release 7510488720Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10488720ReactomeR-GGA-68041161Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-GGA-6804116.1The most prominent TP53 target involved in G1 arrest is the inhibitor of cyclin-dependent kinases CDKN1A (p21). CDKN1A is one of the earliest genes induced by TP53 (El-Deiry et al. 1993). CDKN1A binds and inactivates CDK2 in complex with cyclin A (CCNA) or E (CCNE), thus preventing G1/S transition (Harper et al. 1993). Considering its impact on the cell cycle outcome, CDKN1A expression levels are tightly regulated. For instance, under prolonged stress, TP53 can induce the transcription of an RNA binding protein PCBP4, which can bind and destabilize CDKN1A mRNA, thus alleviating G1 arrest and directing the affected cell towards G2 arrest and, possibly, apoptosis (Zhu and Chen 2000, Scoumanne et al. 2011). Expression of E2F7 is directly induced by TP53. E2F7 contributes to G1 cell cycle arrest by repressing transcription of E2F1, a transcription factor that promotes expression of many genes needed for G1/S transition (Aksoy et al. 2012, Carvajal et al. 2012). ARID3A is a direct transcriptional target of TP53 (Ma et al. 2003) that may promote G1 arrest by cooperating with TP53 in induction of CDKN1A transcription (Lestari et al. 2012). However, ARID3A may also promote G1/S transition by stimulating transcriptional activity of E2F1 (Suzuki et al. 1998, Peeper et al. 2002).<p>TP53 has co-factors that are key determinants of transcriptional selectivity within the p53 network. For instance, the zinc finger transcription factor ZNF385A (HZF) is a direct transcriptional target of TP53 that can form a complex with TP53 and facilitate TP53-mediated induction of CDKN1A, strongly favouring cell cycle arrest over apoptosis (Das et al. 2007). 20817677Pubmed2011The cyclin-dependent kinase inhibitor p21 is regulated by RNA-binding protein PCBP4 via mRNA stabilityScoumanne, ArianeCho, Seong JunZhang, JinChen, XinbinNucleic Acids Res. 39:213-248242752Pubmed1993WAF1, a potential mediator of p53 tumor suppression.el-Deiry, WSTokino, TVelculescu, VELevy, DBParsons, RTrent, JMLin, DMercer, WEKinzler, KWVogelstein, BCell 75:817-2522802529Pubmed2012The atypical E2F family member E2F7 couples the p53 and RB pathways during cellular senescenceAksoy, OzlemChicas, AgustinZeng, TianyingZhao, ZhenMcCurrach, MilaWang, XiaowoLowe, Scott WGenes Dev. 26:1546-5711812999Pubmed2002A functional screen identifies hDRIL1 as an oncogene that rescues RAS-induced senescencePeeper, Daniel SShvarts, AviBrummelkamp, ThijnDouma, SirithKoh, Eugene YDaley, George QBernards, RNat. Cell Biol. 4:148-5322802528Pubmed2012E2F7, a novel target, is up-regulated by p53 and mediates DNA damage-dependent transcriptional repressionCarvajal, Luis AHamard, Pierre-JacquesTonnessen, CrystalManfredi, James JGenes Dev. 26:1533-4512692263Pubmed2003E2FBP1/DRIL1, an AT-rich interaction domain-family transcription factor, is regulated by p53Ma, KaiwenAraki, KeigoIchwan, Solachuddin J ASuganuma, TamakiTamamori-Adachi, MimiIkeda, Masa-AkiMol. Cancer Res. 1:438-4410891498Pubmed2000MCG10, a novel p53 target gene that encodes a KH domain RNA-binding protein, is capable of inducing apoptosis and cell cycle arrest in G(2)-MZhu, JChen, XMol. Cell. Biol. 20:5602-1822172947Pubmed2012Cooperation between ARID3A and p53 in the transcriptional activation of p21WAF1 in response to DNA damageLestari, WidyaIchwan, Solachuddin J AOtsu, MegumiYamada, ShumpeiIseki, SachikoShimizu, ShihokoIkeda, Masa-AkiBiochem. Biophys. Res. Commun. 417:710-617719541Pubmed2007Hzf Determines cell survival upon genotoxic stress by modulating p53 transactivationDas, SanjeevRaj, LakshmiZhao, BoKimura, YukiBernstein, AlanAaronson, Stuart ALee, Sam WCell 130:624-379780002Pubmed1998A novel E2F binding protein with Myc-type HLH motif stimulates E2F-dependent transcription by forming a heterodimerSuzuki, MOkuyama, SOkamoto, SShirasuna, KNakajima, THachiya, TNojima, HSekiya, SOda, KOncogene 17:853-65TP53 Regulates Transcription of Genes Involved in G2 Cell Cycle ArrestThis event has been computationally inferred from an event that has been demonstrated in another species.<p>The inference is based on the homology mapping from PANTHER. Briefly, reactions for which all involved PhysicalEntities (in input, output and catalyst) have a mapped orthologue/paralogue (for complexes at least 75% of components must have a mapping) are inferred to the other species. High level events are also inferred for these events to allow for easier navigation.<p><a href='/electronic_inference_compara.html' target = 'NEW'>More details and caveats of the event inference in Reactome.</a> For details on PANTHER see also: <a href='http://www.pantherdb.org/about.jsp' target='NEW'>http://www.pantherdb.org/about.jsp</a>LEFT-TO-RIGHTGADD45A binds AURKAThis event has been computationally inferred from an event that has been demonstrated in another species.<p>The inference is based on the homology mapping from PANTHER. Briefly, reactions for which all involved PhysicalEntities (in input, output and catalyst) have a mapped orthologue/paralogue (for complexes at least 75% of components must have a mapping) are inferred to the other species. High level events are also inferred for these events to allow for easier navigation.<p><a href='/electronic_inference_compara.html' target = 'NEW'>More details and caveats of the event inference in Reactome.</a> For details on PANTHER see also: <a href='http://www.pantherdb.org/about.jsp' target='NEW'>http://www.pantherdb.org/about.jsp</a>Q2HZD6GADD45AReactome DB_ID: 10471364UniProt:Q2HZD6UniProtQ2HZD61EQUAL165EQUALReactome Database ID Release 7510471364Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10471364ReactomeR-GGA-32151391Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-GGA-3215139.1AURKBAURKAE1BVE1Reactome DB_ID: 10471674UniProt:E1BVE1AURKBUniProtE1BVE11EQUAL403EQUALReactome Database ID Release 7510471674Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10471674ReactomeR-GGA-46554431Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-GGA-4655443.1GADD45A:AURKAReactome DB_ID: 1047167611Reactome Database ID Release 7510471676Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10471676ReactomeR-GGA-67912361Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-GGA-6791236.1Reactome Database ID Release 7510471678Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10471678ReactomeR-GGA-67912351Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-GGA-6791235.1GADD45A binds Aurora-A protein kinase (AURKA). GADD45A inhibits the kinase activity of AURKA and AURKA-induced centrosome amplification, thus interfering with the G2/M transition (Shao et al. 2006, Sanchez et al. 2010).16772293Pubmed2006Gadd45a interacts with aurora-A and inhibits its kinase activityShao, ShujuanWang, YJin, ShunqianSong, YongmeiWang, XiaoxiaFan, WenhongZhao, ZhiyingFu, MingTong, TongDong, LijiaFan, FeiyueXu, NingzhiZhan, QiminJ. Biol. Chem. 281:28943-5020460379Pubmed2010Solution structure of human growth arrest and DNA damage 45alpha (Gadd45alpha) and its interactions with proliferating cell nuclear antigen (PCNA) and Aurora A kinaseSánchez, RicardoPantoja-Uceda, DavidPrieto, JesúsDiercks, TammoMarcaida, María JMontoya, GuillermoCampos-Olivas, RamónBlanco, Francisco JJ. Biol. Chem. 285:22196-201LEFT-TO-RIGHTGADD45A binds PCNAThis event has been computationally inferred from an event that has been demonstrated in another species.<p>The inference is based on the homology mapping from PANTHER. Briefly, reactions for which all involved PhysicalEntities (in input, output and catalyst) have a mapped orthologue/paralogue (for complexes at least 75% of components must have a mapping) are inferred to the other species. High level events are also inferred for these events to allow for easier navigation.<p><a href='/electronic_inference_compara.html' target = 'NEW'>More details and caveats of the event inference in Reactome.</a> For details on PANTHER see also: <a href='http://www.pantherdb.org/about.jsp' target='NEW'>http://www.pantherdb.org/about.jsp</a>PCNA homotrimerReactome DB_ID: 10413625PCNAQ9DEA3Reactome DB_ID: 10413623UniProt:Q9DEA3 PCNAPCNAFUNCTION This protein is an auxiliary protein of DNA polymerase delta and is involved in the control of eukaryotic DNA replication by increasing the polymerase's processibility during elongation of the leading strand.SUBUNIT Homotrimer. Forms a complex with activator 1 heteropentamer in the presence of ATP. Interacts with DNMT1 (By similarity). Interacts with CHAF1A. Component of the replisome complex (By similarity).PTM Monoubiquitinated by the UBE2B-RAD18 complex on Lys-164. Monoubiquitination at Lys-164 also takes place in undamaged proliferating cells, and is mediated by the DCX(DTL) complex, leading to enhance PCNA-dependent translesion DNA synthesis (By similarity).SIMILARITY Belongs to the PCNA family.UniProtQ9DEA31EQUAL261EQUALReactome Database ID Release 7510413623Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10413623ReactomeR-GGA-684391Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-GGA-68439.13Reactome Database ID Release 7510413625Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10413625ReactomeR-GGA-684401Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-GGA-68440.1GADD45A:PCNAReactome DB_ID: 1047136611Reactome Database ID Release 7510471366Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10471366ReactomeR-GGA-67911151Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-GGA-6791115.1Reactome Database ID Release 7510471368Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10471368ReactomeR-GGA-67911091Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-GGA-6791109.1GADD45A binds PCNA homotrimer (Smith et al. 1994, Hall et al. 1995, Sanchez et al. 2010). The consequences of this interaction are not clear. Binding to GADD45A may negatively regulate PCNA-mediated DNA synthesis during S phase of the cell cycle or it may promote PCNA-mediated DNA repair synthesis (Smith et al. 1994, Kim et al. 2013).7784094Pubmed1995Characterisation of the interaction between PCNA and Gadd45Hall, P AKearsey, J MCoates, P JNorman, DGWarbrick, ECox, L SOncogene 10:2427-3323485469Pubmed2013A novel role for Gadd45α in base excision repair: modulation of APE1 activity by the direct interaction of Gadd45α with PCNAKim, Hye LimKim, Sang UkSeo, Young RokBiochem. Biophys. Res. Commun. 434:185-907973727Pubmed1994Interaction of the p53-regulated protein Gadd45 with proliferating cell nuclear antigenSmith, M LChen, I TZhan, QBae, IChen, C YGilmer, T MKastan, M BO'Connor, P MFornace, AJScience 266:1376-80LEFT-TO-RIGHTSFN dimerizesThis event has been computationally inferred from an event that has been demonstrated in another species.<p>The inference is based on the homology mapping from PANTHER. Briefly, reactions for which all involved PhysicalEntities (in input, output and catalyst) have a mapped orthologue/paralogue (for complexes at least 75% of components must have a mapping) are inferred to the other species. High level events are also inferred for these events to allow for easier navigation.<p><a href='/electronic_inference_compara.html' target = 'NEW'>More details and caveats of the event inference in Reactome.</a> For details on PANTHER see also: <a href='http://www.pantherdb.org/about.jsp' target='NEW'>http://www.pantherdb.org/about.jsp</a>2Reactome Database ID Release 7510474875Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10474875ReactomeR-GGA-68038901Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-GGA-6803890.1SFN functions as a homodimer (Verdoodt et al. 2006).17172876Pubmed2006Characterization of 14-3-3sigma dimerization determinants: requirement of homodimerization for inhibition of cell proliferationVerdoodt, BerlindaBenzinger, AnnePopowicz, Grzegorz MHolak, Tad AHermeking, HeikoCell Cycle 5:2920-6Reactome Database ID Release 7510490358Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10490358ReactomeR-GGA-68041141Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-GGA-6804114.1TP53 contributes to the establishment of G2 arrest by inducing transcription of GADD45A and SFN, and by inhibiting transcription of CDC25C. TP53 induces GADD45A transcription in cooperation with chromatin modifying enzymes EP300, PRMT1 and CARM1 (An et al. 2004). GADD45A binds Aurora kinase A (AURKA), inhibiting its catalytic activity and preventing AURKA-mediated G2/M transition (Shao et al. 2006, Sanchez et al. 2010). GADD45A also forms a complex with PCNA. PCNA is involved in both normal and repair DNA synthesis. The effect of GADD45 interaction with PCNA, if any, on S phase progression, G2 arrest and DNA repair is not known (Smith et al. 1994, Hall et al. 1995, Sanchez et al. 2010, Kim et al. 2013). SFN (14-3-3-sigma) is induced by TP53 (Hermeking et al. 1997) and contributes to G2 arrest by binding to the complex of CDK1 and CCNB1 (cyclin B1) and preventing its translocation to the nucleus. Phosphorylation of a number of nuclear proteins by the complex of CDK1 and CCNB1 is needed for G2/M transition (Chan et al. 1999). While promoting G2 arrest, SFN can simultaneously inhibit apoptosis by binding to BAX and preventing its translocation to mitochondria, a step involved in cytochrome C release (Samuel et al. 2001). TP53 binds the promoter of the CDC25C gene in cooperation with the transcriptional repressor E2F4 and represses CDC25C transcription, thus maintaining G2 arrest (St Clair et al. 2004, Benson et al. 2014). The zinc finger transcription factor ZNF385A (HZF) is a direct transcriptional target of TP53 that can form a complex with TP53 and facilitate TP53-mediated induction of SFN transcription (Das et al. 2007).11574543Pubmed2001The G2/M regulator 14-3-3sigma prevents apoptosis through sequestration of BaxSamuel, TWeber, H ORauch, PVerdoodt, BEppel, J TMcShea, AHermeking, HFunk, J OJ. Biol. Chem. 276:45201-624096481Pubmed2014p53-dependent gene repression through p21 is mediated by recruitment of E2F4 repression complexesBenson, E KMungamuri, S KAttie, OKracikova, MSachidanandam, RManfredi, James JAaronson, Stuart AOncogene 33:3959-6910524633Pubmed199914-3-3Sigma is required to prevent mitotic catastrophe after DNA damageChan, T AHermeking, HLengauer, CKinzler, K WVogelstein, BNature 401:616-209659898Pubmed199714-3-3 sigma is a p53-regulated inhibitor of G2/M progressionHermeking, HLengauer, CPolyak, KHe, T CZhang, LThiagalingam, SKinzler, K WVogelstein, BMol. Cell 1:3-1115186775Pubmed2004Ordered cooperative functions of PRMT1, p300, and CARM1 in transcriptional activation by p53An, WoojinKim, JaehoonRoeder, Robert GCell 117:735-4815574328Pubmed2004DNA damage-induced downregulation of Cdc25C is mediated by p53 via two independent mechanisms: one involves direct binding to the cdc25C promoterSt Clair, SelvonGiono, LucianaVarmeh-Ziaie, ShohrehResnick-Silverman, LoisLiu, Wen-JunPadi, AbhilashDastidar, JayasriDaCosta, AndreaMattia, MelissaManfredi, James JMol. Cell 16:725-36TP53 regulates transcription of additional cell cycle genes whose exact role in the p53 pathway remain uncertainThis event has been computationally inferred from an event that has been demonstrated in another species.<p>The inference is based on the homology mapping from PANTHER. Briefly, reactions for which all involved PhysicalEntities (in input, output and catalyst) have a mapped orthologue/paralogue (for complexes at least 75% of components must have a mapping) are inferred to the other species. High level events are also inferred for these events to allow for easier navigation.<p><a href='/electronic_inference_compara.html' target = 'NEW'>More details and caveats of the event inference in Reactome.</a> For details on PANTHER see also: <a href='http://www.pantherdb.org/about.jsp' target='NEW'>http://www.pantherdb.org/about.jsp</a>LEFT-TO-RIGHTBTG2 binds CCR4-NOT complexThis event has been computationally inferred from an event that has been demonstrated in another species.<p>The inference is based on the homology mapping from PANTHER. Briefly, reactions for which all involved PhysicalEntities (in input, output and catalyst) have a mapped orthologue/paralogue (for complexes at least 75% of components must have a mapping) are inferred to the other species. High level events are also inferred for these events to allow for easier navigation.<p><a href='/electronic_inference_compara.html' target = 'NEW'>More details and caveats of the event inference in Reactome.</a> For details on PANTHER see also: <a href='http://www.pantherdb.org/about.jsp' target='NEW'>http://www.pantherdb.org/about.jsp</a>CCR4-NOT ComplexReactome DB_ID: 10436412CNOT10CNOT10Q5ZIW2Reactome DB_ID: 10436374UniProt:Q5ZIW2CNOT10UniProtQ5ZIW21EQUAL744EQUALReactome Database ID Release 7510436374Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10436374ReactomeR-GGA-4298781Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-GGA-429878.11Converted from EntitySet in ReactomeCNOT6 or CNOT6LHomologues of Ccr4Reactome DB_ID: 10436400CNOT6CNOT6A0A1D5P1T8Reactome DB_ID: 10436394UniProt:A0A1D5P1T8CNOT6UniProtA0A1D5P1T81EQUAL557EQUALReactome Database ID Release 7510436394Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10436394ReactomeR-GGA-4299301Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-GGA-429930.1CNOT6LCNOT6LE1C5L3Reactome DB_ID: 10436398UniProt:E1C5L3CNOT6LUniProtE1C5L31EQUAL555EQUALReactome Database ID Release 7510436398Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10436398ReactomeR-GGA-4300271Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-GGA-430027.1Reactome Database ID Release 7510436400Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10436400ReactomeR-GGA-4299621Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-GGA-429962.11Ghost homologue of CNOT3Reactome DB_ID: 10436366Reactome Database ID Release 7510436366Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10436366ReactomeR-GGA-4298721Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-GGA-429872.11CNOT4CNOT4A0A3S5ZP72Reactome DB_ID: 10436370UniProt:A0A3S5ZP72CNOT4UniProtA0A3S5ZP721EQUAL575EQUALReactome Database ID Release 7510436370Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10436370ReactomeR-GGA-4298301Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-GGA-429830.11CNOT2CNOT2Q5ZKI3Reactome DB_ID: 10436378UniProt:Q5ZKI3CNOT2UniProtQ5ZKI31EQUAL540EQUALReactome Database ID Release 7510436378Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10436378ReactomeR-GGA-4299021Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-GGA-429902.11CNOT11CNOT11A0A1D5PEY3Reactome DB_ID: 10436386UniProt:A0A1D5PEY3CNOT11UniProtA0A1D5PEY31EQUAL510EQUALReactome Database ID Release 7510436386Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10436386ReactomeR-GGA-4299811Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-GGA-429981.11TNKS1BP1A0A3Q2U400Reactome DB_ID: 10436390UniProt:A0A3Q2U400UniProtA0A3Q2U4001EQUAL1729EQUALReactome Database ID Release 7510436390Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10436390ReactomeR-GGA-4300111Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-GGA-430011.11Converted from EntitySet in ReactomeCNOT7 or CNOT8Reactome DB_ID: 10436410CNOT7CNOT7Q5ZJV9Reactome DB_ID: 10436404UniProt:Q5ZJV9CNOT7UniProtQ5ZJV91EQUAL285EQUALReactome Database ID Release 7510436404Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10436404ReactomeR-GGA-4298771Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-GGA-429877.1CNOT8CNOT8Q5ZKA9Reactome DB_ID: 10436408UniProt:Q5ZKA9CNOT8UniProtQ5ZKA91EQUAL292EQUALReactome Database ID Release 7510436408Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10436408ReactomeR-GGA-4299791Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-GGA-429979.1Reactome Database ID Release 7510436410Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10436410ReactomeR-GGA-4298681Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-GGA-429868.11RQCD1A0A1D5PVC4Reactome DB_ID: 10436382UniProt:A0A1D5PVC4UniProtA0A1D5PVC41EQUAL299EQUALReactome Database ID Release 7510436382Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10436382ReactomeR-GGA-4300291Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-GGA-430029.11CNOT1CNOT1E1C1B8Reactome DB_ID: 10436364UniProt:E1C1B8CNOT1UniProtE1C1B81EQUAL2376EQUALReactome Database ID Release 7510436364Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10436364ReactomeR-GGA-4298921Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-GGA-429892.11Reactome Database ID Release 7510436412Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10436412ReactomeR-GGA-4298961Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-GGA-429896.1BTG2A0A3Q3AWP4Reactome DB_ID: 10472028UniProt:A0A3Q3AWP4UniProtA0A3Q3AWP41EQUAL158EQUALReactome Database ID Release 7510472028Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10472028ReactomeR-GGA-67980081Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-GGA-6798008.1BTG2:CCR4-NOTReactome DB_ID: 1047203011Reactome Database ID Release 7510472030Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10472030ReactomeR-GGA-67980461Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-GGA-6798046.1Reactome Database ID Release 7510472032Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10472032ReactomeR-GGA-67980441Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-GGA-6798044.1BTG2, through its conserved BTG domain, binds catalytic subunits CNOT7 and CNOT8 of the CCR4-NOT complex and promotes mRNA deadenylation activity of the CCR4-NOT (Rouault et al. 1998, Mauxion et al. 2008, Doidge et al. 2012). The interaction with the CCR4-NOT is needed for the antiproliferative activity of BTG2 (Horiuchi et al. 2009, Doidge et al. 2012, Ezzeddine et al. 2012).18337750Pubmed2008The BTG2 protein is a general activator of mRNA deadenylationMauxion, FabienneFaux, CélineSéraphin, BertrandEMBO J. 27:1039-4819276069Pubmed2009Structural basis for the antiproliferative activity of the Tob-hCaf1 complexHoriuchi, MasatakaTakeuchi, KoseiNoda, NobuoMuroya, NobuyukiSuzuki, ToruNakamura, TakahisaKawamura-Tsuzuku, JunkoTakahasi, KiyohiroYamamoto, TadashiInagaki, FJ. Biol. Chem. 284:13244-5522252318Pubmed2012Evidence providing new insights into TOB-promoted deadenylation and supporting a link between TOB's deadenylation-enhancing and antiproliferative activitiesEzzeddine, NaderChen, Chyi-Ying AShyu, Ann-BinMol. Cell. Biol. 32:1089-989712883Pubmed1998Interaction of BTG1 and p53-regulated BTG2 gene products with mCaf1, the murine homolog of a component of the yeast CCR4 transcriptional regulatory complexRouault, J PPrévôt, DBerthet, CBirot, A MBillaud, MMagaud, J PCorbo, LJ. Biol. Chem. 273:22563-923236473Pubmed2012The anti-proliferative activity of BTG/TOB proteins is mediated via the Caf1a (CNOT7) and Caf1b (CNOT8) deadenylase subunits of the Ccr4-not complexDoidge, RachelMittal, SaloniAslam, AkhmedWinkler, G SebastiaanPLoS ONE 7:e51331LEFT-TO-RIGHT2.7.11PLK2 phosphorylates CENPJThis event has been computationally inferred from an event that has been demonstrated in another species.<p>The inference is based on the homology mapping from PANTHER. Briefly, reactions for which all involved PhysicalEntities (in input, output and catalyst) have a mapped orthologue/paralogue (for complexes at least 75% of components must have a mapping) are inferred to the other species. High level events are also inferred for these events to allow for easier navigation.<p><a href='/electronic_inference_compara.html' target = 'NEW'>More details and caveats of the event inference in Reactome.</a> For details on PANTHER see also: <a href='http://www.pantherdb.org/about.jsp' target='NEW'>http://www.pantherdb.org/about.jsp</a>CENPJE1C0R8Reactome DB_ID: 10432872UniProt:E1C0R8UniProtE1C0R81EQUAL1338EQUALReactome Database ID Release 7510432872Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10432872ReactomeR-GGA-3802911Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-GGA-380291.12E1C0R8phospho-p-S589,S595-CENPJReactome DB_ID: 10474742589EQUAL595EQUAL1EQUAL1338EQUALReactome Database ID Release 7510474742Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10474742ReactomeR-GGA-68016701Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-GGA-6801670.12ACTIVATIONPLK2PLK2F1NB57Reactome DB_ID: 10474746UniProt:F1NB57PLK2UniProtF1NB571EQUAL685EQUALReactome Database ID Release 7510474746Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10474746ReactomeR-GGA-68016361Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-GGA-6801636.1Reactome Database ID Release 7510474747Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10474747Reactome Database ID Release 7510474749Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10474749ReactomeR-GGA-68016661Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-GGA-6801666.1PLK2 phosphorylates centrosome protein CENPJ (CPAP) on serine residues S589 and S585, which is a prerequisite for procentriole formation and centrosome duplication (Chang et al. 2010).20531387Pubmed2010PLK2 phosphorylation is critical for CPAP function in procentriole formation during the centrosome cycleChang, JaerakCizmecioglu, OnurHoffmann, IngridRhee, KunsooEMBO J. 29:2395-406LEFT-TO-RIGHT2.7.11PLK2 phosphorylates NPM1This event has been computationally inferred from an event that has been demonstrated in another species.<p>The inference is based on the homology mapping from PANTHER. Briefly, reactions for which all involved PhysicalEntities (in input, output and catalyst) have a mapped orthologue/paralogue (for complexes at least 75% of components must have a mapping) are inferred to the other species. High level events are also inferred for these events to allow for easier navigation.<p><a href='/electronic_inference_compara.html' target = 'NEW'>More details and caveats of the event inference in Reactome.</a> For details on PANTHER see also: <a href='http://www.pantherdb.org/about.jsp' target='NEW'>http://www.pantherdb.org/about.jsp</a>NPM1A0A1L1RJ78Reactome DB_ID: 10474751UniProt:A0A1L1RJ78UniProtA0A1L1RJ781EQUAL294EQUALReactome Database ID Release 7510474751Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10474751ReactomeR-GGA-30082111Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-GGA-3008211.1A0A1L1RJ78phospho-p-S4-NPM1Reactome DB_ID: 104747544EQUAL1EQUAL294EQUALReactome Database ID Release 7510474754Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10474754ReactomeR-GGA-68016791Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-GGA-6801679.1ACTIVATIONReactome Database ID Release 7510474756Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10474756ReactomeR-GGA-68016751Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-GGA-6801675.1PLK2 phosphorylates NPM1 (nucleophosmin) on serine residue S4, which may be necessary to trigger centrosome duplication (Krause and Hoffmann 2010).20352051Pubmed2010Polo-like kinase 2-dependent phosphorylation of NPM/B23 on serine 4 triggers centriole duplicationKrause, AnnekatrinHoffmann, IngridPLoS ONE 5:e9849Reactome Database ID Release 7510490370Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10490370ReactomeR-GGA-68041151Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-GGA-6804115.1BTG2 is induced by TP53, leading to cessation of cellular proliferation (Rouault et al. 1996, Duriez et al. 2002). BTG2 binds to the CCR4-NOT complex and promotes mRNA deadenylation activity of this complex. Interaction between BTG2 and CCR4-NOT is needed for the antiproliferative activity of BTG2, but the underlying mechanism has not been elucidated (Rouault et al. 1998, Mauxion et al. 2008, Horiuchi et al. 2009, Doidge et al. 2012, Ezzeddine et al. 2012). Two polo-like kinases, PLK2 and PLK3, are direct transcriptional targets of TP53. TP53-mediated induction of PLK2 may be important for prevention of mitotic catastrophe after spindle damage (Burns et al. 2003). PLK2 is involved in the regulation of centrosome duplication through phosphorylation of centrosome-related proteins CENPJ (Chang et al. 2010) and NPM1 (Krause and Hoffmann 2010). PLK2 is frequently transcriptionally silenced through promoter methylation in B-cell malignancies (Syed et al. 2006). Induction of PLK3 transcription by TP53 (Jen and Cheung 2005) may be important for coordination of M phase events through PLK3-mediated nuclear accumulation of CDC25C (Bahassi et al. 2004). RGCC is induced by TP53 and implicated in cell cycle regulation, possibly through its association with PLK1 (Saigusa et al. 2007). PLAGL1 (ZAC1) is a zinc finger protein directly transcriptionally induced by TP53 (Rozenfeld-Granot et al. 2002). PLAGL1 expression is frequently lost in cancer (Varrault et al. 1998) and PLAGL1 has been implicated in both cell cycle arrest and apoptosis (Spengler et al. 1997), but its mechanism of action remains unknown.8944033Pubmed1996Identification of BTG2, an antiproliferative p53-dependent component of the DNA damage cellular response pathwayRouault, J PFalette, NGuéhenneux, FGuillot, CRimokh, RWang, QBerthet, CMoyret-Lalle, CSavatier, PPain, BShaw, PBerger, RSamarut, JMagaud, J POzturk, MSamarut, CPuisieux, ANat. Genet. 14:482-616160013Pubmed2006Transcriptional silencing of Polo-like kinase 2 (SNK/PLK2) is a frequent event in B-cell malignanciesSyed, NeloferSmith, PaulSullivan, AlexandraSpender, Lindsay CDyer, MartinKarran, LorraineO'Nions, JennyAllday, MartinHoffmann, IngridCrawford, DorothyGriffin, BeverleyFarrell, Paul JCrook, TimBlood 107:250-612897130Pubmed2003Silencing of the novel p53 target gene Snk/Plk2 leads to mitotic catastrophe in paclitaxel (taxol)-exposed cellsBurns, Timothy FFei, PeiwenScata, Kimberly ADicker, David TEl-Deiry, Wafik SMol. Cell. Biol. 23:5556-719671765Pubmed1998hZAC encodes a zinc finger protein with antiproliferative properties and maps to a chromosomal region frequently lost in cancerVarrault, ACiani, EApiou, FBilanges, BHoffmann, APantaloni, CBockaert, JSpengler, DJournot, LProc. Natl. Acad. Sci. U.S.A. 95:8835-4011896574Pubmed2002A positive feedback mechanism in the transcriptional activation of Apaf-1 by p53 and the coactivator Zac-1Rozenfeld-Granot, GalitKrishnamurthy, JanakiramanKannan, KaruppiahToren, AmosAmariglio, NinetteGivol, DavidRechavi, GideonOncogene 21:1469-769184226Pubmed1997Regulation of apoptosis and cell cycle arrest by Zac1, a novel zinc finger protein expressed in the pituitary gland and the brainSpengler, DVillalba, MHoffmann, APantaloni, CHoussami, SBockaert, JJournot, LEMBO J. 16:2814-2514968113Pubmed2004Cdc25C phosphorylation on serine 191 by Plk3 promotes its nuclear translocationBahassi, El MustaphaHennigan, Robert FMyer, David LStambrook, Peter JOncogene 23:2658-6311814693Pubmed2002The human BTG2/TIS21/PC3 gene: genomic structure, transcriptional regulation and evaluation as a candidate tumor suppressor geneDuriez, CyrilFalette, NicoleAudoynaud, CaroleMoyret-Lalle, CarolineBensaad, KarimCourtois, StéphanieWang, QSoussi, ThierryPuisieux, AlainGene 282:207-1417146433Pubmed2007RGC32, a novel p53-inducible gene, is located on centrosomes during mitosis and results in G2/M arrestSaigusa, KImoto, ITanikawa, CAoyagi, MOhno, KNakamura, YInazawa, JOncogene 26:1110-21Reactome Database ID Release 7510488722Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10488722ReactomeR-GGA-67913121Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-GGA-6791312.1GENE ONTOLOGYGO:0006977Under a variety of stress conditions, TP53 (p53), stabilized by stress-induced phosphorylation at least on S15 and S20 serine residues, can induce the transcription of genes involved in cell cycle arrest. Cell cycle arrest provides cells an opportunity to repair the damage before division, thus preventing the transmission of genetic errors to daughter cells. In addition, it allows cells to attempt a recovery from the damage and survive, preventing premature cell death.<p>TP53 controls transcription of genes involved in both G1 and G2 cell cycle arrest. The most prominent TP53 target involved in G1 arrest is the inhibitor of cyclin-dependent kinases CDKN1A (p21). CDKN1A is one of the earliest genes induced by TP53 (El-Deiry et al. 1993). CDKN1A binds and inactivates CDK2 in complex with cyclin A (CCNA) or E (CCNE), thus preventing G1/S transition (Harper et al. 1993). Nevertheless, under prolonged stress, the cell destiny may be diverted towards an apoptotic outcome. For instance, in case of an irreversible damage, TP53 can induce transcription of an RNA binding protein PCBP4, which can bind and destabilize CDKN1A mRNA, thus alleviating G1 arrest and directing the affected cell towards G2 arrest and, possibly, apoptosis (Zhu and Chen 2000, Scoumanne et al. 2011). Expression of E2F7 is directly induced by TP53. E2F7 contributes to G1 cell cycle arrest by repressing transcription of E2F1, a transcription factor that promotes expression of many genes needed for G1/S transition (Aksoy et al. 2012, Carvajal et al. 2012). ARID3A is a direct transcriptional target of TP53 (Ma et al. 2003) that may promote G1 arrest by cooperating with TP53 in induction of CDKN1A transcription (Lestari et al. 2012). However, ARID3A may also promote G1/S transition by stimulating transcriptional activity of E2F1 (Suzuki et al. 1998, Peeper et al. 2002).<p>TP53 contributes to the establishment of G2 arrest by inducing transcription of GADD45A and SFN, and by inhibiting transcription of CDC25C. TP53 induces GADD45A transcription in cooperation with chromatin modifying enzymes EP300, PRMT1 and CARM1 (An et al. 2004). GADD45A binds Aurora kinase A (AURKA), inhibiting its catalytic activity and preventing AURKA-mediated G2/M transition (Shao et al. 2006, Sanchez et al. 2010). GADD45A also forms a complex with PCNA. PCNA is involved in both normal and repair DNA synthesis. The effect of GADD45 interaction with PCNA, if any, on S phase progression, G2 arrest and DNA repair is not known (Smith et al. 1994, Hall et al. 1995, Sanchez et al. 2010, Kim et al. 2013). SFN (14-3-3-sigma) is induced by TP53 (Hermeking et al. 1997) and contributes to G2 arrest by binding to the complex of CDK1 and CCNB1 (cyclin B1) and preventing its translocation to the nucleus. Phosphorylation of a number of nuclear proteins by the complex of CDK1 and CCNB1 is needed for G2/M transition (Chan et al. 1999). While promoting G2 arrest, SFN can simultaneously inhibit apoptosis by binding to BAX and preventing its translocation to mitochondria, a step involved in cytochrome C release (Samuel et al. 2001). TP53 binds the promoter of the CDC25C gene in cooperation with the transcriptional repressor E2F4 and represses CDC25C transcription, thus maintaining G2 arrest (St Clair et al. 2004, Benson et al. 2014).<p>Several direct transcriptional targets of TP53 are involved in cell cycle arrest but their mechanism of action is still unknown. BTG2 is induced by TP53, leading to cessation of cellular proliferation (Rouault et al. 1996, Duriez et al. 2002). BTG2 binds to the CCR4-NOT complex and promotes mRNA deadenylation activity of this complex. Interaction between BTG2 and CCR4-NOT is needed for the antiproliferative activity of BTG2, but the underlying mechanism has not been elucidated (Rouault et al. 1998, Mauxion et al. 2008, Horiuchi et al. 2009, Doidge et al. 2012, Ezzeddine et al. 2012). Two polo-like kinases, PLK2 and PLK3, are direct transcriptional targets of TP53. TP53-mediated induction of PLK2 may be important for prevention of mitotic catastrophe after spindle damage (Burns et al. 2003). PLK2 is involved in the regulation of centrosome duplication through phosphorylation of centrosome-related proteins CENPJ (Chang et al. 2010) and NPM1 (Krause and Hoffmann 2010). PLK2 is frequently transcriptionally silenced through promoter methylation in B-cell malignancies (Syed et al. 2006). Induction of PLK3 transcription by TP53 (Jen and Cheung 2005) may be important for coordination of M phase events through PLK3-mediated nuclear accumulation of CDC25C (Bahassi et al. 2004). RGCC is induced by TP53 and implicated in cell cycle regulation, possibly through its association with PLK1 (Saigusa et al. 2007). PLAGL1 (ZAC1) is a zinc finger protein directly transcriptionally induced by TP53 (Rozenfeld-Granot et al. 2002). PLAGL1 expression is frequently lost in cancer (Varrault et al. 1998) and PLAGL1 has been implicated in both cell cycle arrest and apoptosis (Spengler et al. 1997), but its mechanism of action remains unknown.<p>The zinc finger transcription factor ZNF385A (HZF) is a direct transcriptional target of TP53 that can form a complex with TP53 and facilitate TP53-mediated induction of CDKN1A and SFN (14-3-3 sigma) transcription (Das et al. 2007).<p>For a review of the role of TP53 in cell cycle arrest and cell cycle transcriptional targets of TP53, please refer to Riley et al. 2008, Murray-Zmijewski et al. 2008, Bieging et al. 2014, Kruiswijk et al. 2015.TP53 Regulates Transcription of DNA Repair GenesThis event has been computationally inferred from an event that has been demonstrated in another species.<p>The inference is based on the homology mapping from PANTHER. Briefly, reactions for which all involved PhysicalEntities (in input, output and catalyst) have a mapped orthologue/paralogue (for complexes at least 75% of components must have a mapping) are inferred to the other species. High level events are also inferred for these events to allow for easier navigation.<p><a href='/electronic_inference_compara.html' target = 'NEW'>More details and caveats of the event inference in Reactome.</a> For details on PANTHER see also: <a href='http://www.pantherdb.org/about.jsp' target='NEW'>http://www.pantherdb.org/about.jsp</a>LEFT-TO-RIGHTCCNK binds CDK12This event has been computationally inferred from an event that has been demonstrated in another species.<p>The inference is based on the homology mapping from PANTHER. Briefly, reactions for which all involved PhysicalEntities (in input, output and catalyst) have a mapped orthologue/paralogue (for complexes at least 75% of components must have a mapping) are inferred to the other species. High level events are also inferred for these events to allow for easier navigation.<p><a href='/electronic_inference_compara.html' target = 'NEW'>More details and caveats of the event inference in Reactome.</a> For details on PANTHER see also: <a href='http://www.pantherdb.org/about.jsp' target='NEW'>http://www.pantherdb.org/about.jsp</a>CDK12E1BUG0Reactome DB_ID: 10471816UniProt:E1BUG0UniProtE1BUG01EQUAL1490EQUALReactome Database ID Release 7510471816Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10471816ReactomeR-GGA-67970121Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-GGA-6797012.1CCNKCCNKF1NCA1Reactome DB_ID: 10419240UniProt:F1NCA1CCNKUniProtF1NCA11EQUAL580EQUALReactome Database ID Release 7510419240Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10419240ReactomeR-GGA-67966191Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-GGA-6796619.1CCNK:CDK12Reactome DB_ID: 1047181811Reactome Database ID Release 7510471818Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10471818ReactomeR-GGA-67970951Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-GGA-6797095.1Reactome Database ID Release 7510471820Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10471820ReactomeR-GGA-67970901Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-GGA-6797090.1Cyclin K (CCNK) forms a complex with CDK12 (Blazek et al. 2011).22012619Pubmed2011The Cyclin K/Cdk12 complex maintains genomic stability via regulation of expression of DNA damage response genesBlazek, DaliborKohoutek, JiriBartholomeeusen, KoenJohansen, EricHulinkova, PetraLuo, ZepingCimermancic, PeterUle, JernejPeterlin, B MatijaGenes Dev. 25:2158-72LEFT-TO-RIGHTCCNK binds CDK13This event has been computationally inferred from an event that has been demonstrated in another species.<p>The inference is based on the homology mapping from PANTHER. Briefly, reactions for which all involved PhysicalEntities (in input, output and catalyst) have a mapped orthologue/paralogue (for complexes at least 75% of components must have a mapping) are inferred to the other species. High level events are also inferred for these events to allow for easier navigation.<p><a href='/electronic_inference_compara.html' target = 'NEW'>More details and caveats of the event inference in Reactome.</a> For details on PANTHER see also: <a href='http://www.pantherdb.org/about.jsp' target='NEW'>http://www.pantherdb.org/about.jsp</a>CDK13A0A1D5PTK4Reactome DB_ID: 10471824UniProt:A0A1D5PTK4UniProtA0A1D5PTK41EQUAL1512EQUALReactome Database ID Release 7510471824Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10471824ReactomeR-GGA-67970141Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-GGA-6797014.1CCNK:CDK13Reactome DB_ID: 1047182611Reactome Database ID Release 7510471826Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10471826ReactomeR-GGA-67970941Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-GGA-6797094.1Reactome Database ID Release 7510471828Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10471828ReactomeR-GGA-67971001Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-GGA-6797100.1Cyclin K (CCNK) forms a complex with CDK13 (Blazek et al. 2011).LEFT-TO-RIGHTCCNK:CDK12 binds RNA Pol II at DNA repair genesThis event has been computationally inferred from an event that has been demonstrated in another species.<p>The inference is based on the homology mapping from PANTHER. Briefly, reactions for which all involved PhysicalEntities (in input, output and catalyst) have a mapped orthologue/paralogue (for complexes at least 75% of components must have a mapping) are inferred to the other species. High level events are also inferred for these events to allow for easier navigation.<p><a href='/electronic_inference_compara.html' target = 'NEW'>More details and caveats of the event inference in Reactome.</a> For details on PANTHER see also: <a href='http://www.pantherdb.org/about.jsp' target='NEW'>http://www.pantherdb.org/about.jsp</a>Elongation Complex at DNA Repair GenesReactome DB_ID: 10471922FACT complexReactome DB_ID: 10419323Ghost homologue of SUPT16HReactome DB_ID: 10419321Reactome Database ID Release 7510419321Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10419321ReactomeR-GGA-1124151Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-GGA-112415.11SSRP1B6ZLK1Reactome DB_ID: 10419319UniProt:B6ZLK1UniProtB6ZLK12EQUAL709EQUALReactome Database ID Release 7510419319Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10419319ReactomeR-GGA-651051Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-GGA-65105.11Reactome Database ID Release 7510419323Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10419323ReactomeR-GGA-1124171Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-GGA-112417.11TCEA1TCEA1Q5ZHQ8Reactome DB_ID: 10419304UniProt:Q5ZHQ8TCEA1UniProtQ5ZHQ81EQUAL301EQUALReactome Database ID Release 7510419304Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10419304ReactomeR-GGA-657481Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-GGA-65748.11Hyperphosphorylated RNA Pol II at DNA repair genesReactome DB_ID: 10471920DSIF complexReactome DB_ID: 10419272Ghost homologue of p-SUPT5HReactome DB_ID: 10417934Reactome Database ID Release 7510417934Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10417934ReactomeR-GGA-30093721Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-GGA-3009372.11SUPT4H1SUPT4H1A0A3Q2TZR8Reactome DB_ID: 10419270UniProt:A0A3Q2TZR8SUPT4H1UniProtA0A3Q2TZR81EQUAL117EQUALReactome Database ID Release 7510419270Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10419270ReactomeR-GGA-649051Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-GGA-64905.11Reactome Database ID Release 7510419272Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10419272ReactomeR-GGA-1124201Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-GGA-112420.11CTDP1A0A3Q2U767Reactome DB_ID: 10419276UniProt:A0A3Q2U767UniProtA0A3Q2U7671EQUAL961EQUALReactome Database ID Release 7510419276Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10419276ReactomeR-GGA-1134161Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-GGA-113416.11P-TEFb complexReactome DB_ID: 10419248Converted from EntitySet in ReactomeCCNT1,CCNT2,CCNKReactome DB_ID: 10419246CCNT1CCNT1A0A3Q3ACK9Reactome DB_ID: 10419244UniProt:A0A3Q3ACK9CCNT1UniProtA0A3Q3ACK91EQUAL726EQUALReactome Database ID Release 7510419244Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10419244ReactomeR-GGA-516111Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-GGA-51611.1Reactome Database ID Release 7510419246Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10419246ReactomeR-GGA-68074661Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-GGA-6807466.11CDK9A0A452J859Reactome DB_ID: 10419236UniProt:A0A452J859UniProtA0A452J8591EQUAL372EQUALReactome Database ID Release 7510419236Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10419236ReactomeR-GGA-518011Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-GGA-51801.11Reactome Database ID Release 7510419248Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10419248ReactomeR-GGA-1124311Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-GGA-112431.11Ghost homologue of Nascent mRNAs of DNA repair genes regulated by CDK12Reactome DB_ID: 10471918Reactome Database ID Release 7510471918Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10471918ReactomeR-GGA-67976041Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-GGA-6797604.11NELF complexReactome DB_ID: 10419266NELFANELFAF1NCM6Reactome DB_ID: 10419252UniProt:F1NCM6NELFAUniProtF1NCM61EQUAL528EQUALReactome Database ID Release 7510419252Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10419252ReactomeR-GGA-1124261Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-GGA-112426.11NELFBNELFBQ5ZLK9Reactome DB_ID: 10419256UniProt:Q5ZLK9NELFBUniProtQ5ZLK91EQUAL580EQUALReactome Database ID Release 7510419256Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10419256ReactomeR-GGA-1124271Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-GGA-112427.11NELFCDNELFCDQ5ZIQ8Reactome DB_ID: 10419260UniProt:Q5ZIQ8NELFCDUniProtQ5ZIQ81EQUAL590EQUALReactome Database ID Release 7510419260Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10419260ReactomeR-GGA-1124281Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-GGA-112428.11NELFENELFEA0A3Q2UGX9Reactome DB_ID: 10419264UniProt:A0A3Q2UGX9NELFEUniProtA0A3Q2UGX91EQUAL380EQUALReactome Database ID Release 7510419264Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10419264ReactomeR-GGA-629071Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-GGA-62907.11Reactome Database ID Release 7510419266Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10419266ReactomeR-GGA-1124321Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-GGA-112432.11Ghost homologue of DNA repair genes regulated by CDK12Reactome DB_ID: 10471916Reactome Database ID Release 7510471916Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10471916ReactomeR-GGA-67976151Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-GGA-6797615.11RNA Polymerase II holoenzyme complex (hyperphosphorylated):TFIIF complexReactome DB_ID: 10419232TFIIFReactome DB_ID: 10415038Ghost homologue of GTF2F1Reactome DB_ID: 10415032Reactome Database ID Release 7510415032Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10415032ReactomeR-GGA-655651Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-GGA-65565.11GTF2F2GTF2F2E1BXD0Reactome DB_ID: 10415036UniProt:E1BXD0GTF2F2UniProtE1BXD02EQUAL249EQUALReactome Database ID Release 7510415036Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10415036ReactomeR-GGA-655671Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-GGA-65567.11Reactome Database ID Release 7510415038Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10415038ReactomeR-GGA-1096311Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-GGA-109631.11RNA Polymerase II holoenzyme complex (hyperphosphorylated)Reactome DB_ID: 10419230POLR2IPOLR2IA0A1D5PEI0Reactome DB_ID: 10414994UniProt:A0A1D5PEI0POLR2IUniProtA0A1D5PEI01EQUAL125EQUALReactome Database ID Release 7510414994Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10414994ReactomeR-GGA-635251Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-GGA-63525.11POLR2DPOLR2DF1P2S1Reactome DB_ID: 10415002UniProt:F1P2S1POLR2DUniProtF1P2S11EQUAL142EQUALReactome Database ID Release 7510415002Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10415002ReactomeR-GGA-635081Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-GGA-63508.11Ghost homologue of POLR2GReactome DB_ID: 10415004Reactome Database ID Release 7510415004Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10415004ReactomeR-GGA-635171Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-GGA-63517.11POLR2LPOLR2LE1BSY6Reactome DB_ID: 10415028UniProt:E1BSY6POLR2LUniProtE1BSY61EQUAL67EQUALReactome Database ID Release 7510415028Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10415028ReactomeR-GGA-837151Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-GGA-83715.11POLR2FQ9PT88Reactome DB_ID: 10415024UniProt:Q9PT88UniProtQ9PT882EQUAL127EQUALReactome Database ID Release 7510415024Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10415024ReactomeR-GGA-837141Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-GGA-83714.11Ghost homologue of p-S2,S5-POLR2AReactome DB_ID: 10419228Reactome Database ID Release 7510419228Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10419228ReactomeR-GGA-1134201Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-GGA-113420.11POLR2CPOLR2CE1BV97Reactome DB_ID: 10415008UniProt:E1BV97POLR2CUniProtE1BV972EQUAL275EQUALReactome Database ID Release 7510415008Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10415008ReactomeR-GGA-635061Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-GGA-63506.11POLR2KA0A1D5P7C5Reactome DB_ID: 10415016UniProt:A0A1D5P7C5UniProtA0A1D5P7C51EQUAL58EQUALReactome Database ID Release 7510415016Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10415016ReactomeR-GGA-635371Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-GGA-63537.11POLR2JA0A1D5NWZ8Reactome DB_ID: 10414990UniProt:A0A1D5NWZ8UniProtA0A1D5NWZ81EQUAL117EQUALReactome Database ID Release 7510414990Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10414990ReactomeR-GGA-635311Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-GGA-63531.11POLR2BPOLR2BF1NCB0Reactome DB_ID: 10414998UniProt:F1NCB0POLR2BUniProtF1NCB01EQUAL1174EQUALReactome Database ID Release 7510414998Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10414998ReactomeR-GGA-635041Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-GGA-63504.11POLR2EPOLR2EF1NHV9Reactome DB_ID: 10415020UniProt:F1NHV9POLR2EUniProtF1NHV91EQUAL210EQUALReactome Database ID Release 7510415020Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10415020ReactomeR-GGA-837131Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-GGA-83713.11POLR2HA0A3Q2TVW3Reactome DB_ID: 10415012UniProt:A0A3Q2TVW3UniProtA0A3Q2TVW32EQUAL150EQUALReactome Database ID Release 7510415012Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10415012ReactomeR-GGA-635231Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-GGA-63523.11Reactome Database ID Release 7510419230Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10419230ReactomeR-GGA-1099091Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-GGA-109909.11Reactome Database ID Release 7510419232Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10419232ReactomeR-GGA-1134251Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-GGA-113425.11Reactome Database ID Release 7510471920Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10471920ReactomeR-GGA-67976091Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-GGA-6797609.11TFIIHReactome DB_ID: 10416407Ghost homologue of ERCC2Reactome DB_ID: 10416384Reactome Database ID Release 7510416384Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10416384ReactomeR-GGA-674431Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-GGA-67443.11GTF2H2GTF2H2E1C9E6Reactome DB_ID: 10416396UniProt:E1C9E6GTF2H2UniProtE1C9E61EQUAL395EQUALReactome Database ID Release 7510416396Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10416396ReactomeR-GGA-659141Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-GGA-65914.11ERCC3ERCC3F1NZ23Reactome DB_ID: 10416388