BioPAX pathway converted from "Transcriptional Regulation by TP53" in the Reactome database.Transcriptional Regulation by TP53Transcriptional 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 GenesTP53 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>3.1.3.46TIGAR converts D-fructose-2,6-bisphosphate to D-fructose 6-phosphateTIGAR 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>Reactome DB_ID: 305331cytosolGO0005829beta-D-fructofuranose 2,6-bisphosphate [ChEBI:28602]beta-D-fructofuranose 2,6-bisphosphateReactomehttp://www.reactome.orgChEBI28602Reactome DB_ID: 293561water [ChEBI:15377]waterChEBI15377Reactome DB_ID: 295121beta-D-fructofuranose 6-phosphate(2-) [ChEBI:57634]beta-D-fructofuranose 6-phosphate(2-)6-O-phosphonato-beta-D-fructofuranosebeta-D-fructofuranose 6-phosphate dianionChEBI57634Reactome DB_ID: 293721hydrogenphosphate [ChEBI:43474]hydrogenphosphate[PO3(OH)](2-)HYDROGENPHOSPHATE IONhydrogen phosphate[P(OH)O3](2-)HPO4(2-)phosphateINORGANIC PHOSPHATE GROUPChEBI43474PHYSIOL-LEFT-TO-RIGHTACTIVATIONReactome DB_ID: 10269442UniProt:Q29RA5tigaraDanio rerioNCBI Taxonomy7955UniProtQ29RA5Chain Coordinates1EQUAL270EQUALGO0004331GO molecular functionReactome Database ID Release 7510269443Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10269443Reactome Database ID Release 7510269445Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10269445ReactomeR-DRE-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-DRE-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 by electronic annotationIEAGOIEA5.3.1.9D-fructose 6-phosphate <=> alpha-D-Glucose 6-phosphateD-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>Reactome DB_ID: 295121Reactome DB_ID: 305371alpha-D-glucose 6-phosphate(2-) [ChEBI:58225]alpha-D-glucose 6-phosphate(2-)alpha-D-glucose 6-phosphate dianionalpha-D-glucopyranose 6-phosphate6-O-phosphonato-alpha-D-glucopyranosealpha-D-glucose 6-phosphateChEBI58225PHYSIOL-LEFT-TO-RIGHTACTIVATIONReactome DB_ID: 10189761GPI dimer [cytosol]GPI dimerReactome DB_ID: 101897592UniProt:A8DZE4gpibUniProtA8DZE42EQUAL558EQUALReactome Database ID Release 7510189761Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10189761ReactomeR-DRE-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-DRE-70469.1GO0004347GO molecular functionReactome Database ID Release 7510189762Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10189762Reactome Database ID Release 7510189766Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10189766ReactomeR-DRE-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-DRE-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 231:19-29inferred by electronic annotationIEAGOIEA1.1.1.49alpha-D-glucose 6-phosphate + NADP+ => D-glucono-1,5-lactone 6-phosphate + NADPH + H+alpha-D-glucose 6-phosphate + NADP+ => D-glucono-1,5-lactone 6-phosphate + NADPH + H+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>Reactome DB_ID: 305371Reactome DB_ID: 293661NADP(+) [ChEBI:18009]NADP(+)ChEBI18009Reactome DB_ID: 3146716-O-phosphono-D-glucono-1,5-lactone [ChEBI:16938]6-O-phosphono-D-glucono-1,5-lactoneChEBI16938Reactome DB_ID: 293641NADPH [ChEBI:16474]NADPHTPNHChEBI16474Reactome DB_ID: 701061hydron [ChEBI:15378]hydronChEBI15378PHYSIOL-LEFT-TO-RIGHTACTIVATIONConverted from EntitySet in ReactomeReactome DB_ID: 10189670G6PD dimer and tetramer [cytosol]Converted from EntitySet in Reactome. Each synonym is a name of a PhysicalEntity, and each XREF points to one PhysicalEntityGO0004345GO molecular functionReactome Database ID Release 7510189671Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10189671Reactome Database ID Release 7510189673Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10189673ReactomeR-DRE-703771Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-DRE-70377.1Cytosolic glucose-6-phosphate dehydrogenase (G6PD) catalyzes the reaction of glucose 6-phosphate and NADP+ to form D-glucono-1,5-lactone 6-phosphate and NADPH + H+. This constitutes the first committed step of the pentose phosphate pathway and it is critical to the maintenance of NAPDH pool and redox homeostasis. For this reason, anti-cancer therapies are making this step as a prominent target in cancer therapy (Zhang et al. 2014). The reaction is inhibited by high ADP/AMP concentration, and by high NAPDH concentration. Biochemical studies indicate that both G6PD dimers and tetramers are catalytically active and present under physiological conditions in vivo (Au et al. 2000). Mutations that reduce the catalytic efficiency of G6PD are remarkably common in human populations; these appear to have a protective effect against malaria (e.g., Luzzatto and Afolayan 1968).10745013Pubmed2000Human glucose-6-phosphate dehydrogenase: the crystal structure reveals a structural NADP(+) molecule and provides insights into enzyme deficiencyAu, SWGover, SLam, VMAdams, MJStructure 8:293-30324066844Pubmed2014Glucose-6-phosphate dehydrogenase: a biomarker and potential therapeutic target for cancerZhang, ChunhuaZhang, ZhengZhu, YuechunQin, SuofuAnticancer Agents Med Chem 14:280-95666113Pubmed1968Enzymic properties of different types of human erythrocyte glucose-6-phosphate dehydrogenase, with characterization of two new genetic variantsLuzzatto, LAfolayan, AJ Clin Invest 47:1833-42inferred by electronic annotationIEAGOIEA1.8.1.7glutathione (oxidized) + NADPH + H+ => 2 glutathione (reduced) + NADP+glutathione (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>Reactome DB_ID: 293641Reactome DB_ID: 1117451glutathione disulfide [ChEBI:17858]glutathione disulfideChEBI17858Reactome DB_ID: 701061Reactome DB_ID: 294502glutathione [ChEBI:16856]glutathioneChEBI16856Reactome DB_ID: 293661PHYSIOL-LEFT-TO-RIGHTACTIVATIONReactome DB_ID: 10190895GSR-2:FAD dimer [cytosol]GSR-2:FAD dimerReactome DB_ID: 293862FAD [ChEBI:16238]FADFlavin adenine dinucleotideChEBI16238Reactome DB_ID: 101908932UniProt:A0A2R8RQT4gsrUniProtA0A2R8RQT444EQUAL522EQUALReactome Database ID Release 7510190895Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10190895ReactomeR-DRE-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-DRE-71680.1GO0004362GO molecular functionReactome Database ID Release 7510190896Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10190896Reactome Database ID Release 7510190898Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10190898ReactomeR-DRE-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-DRE-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 48:53-62inferred by electronic annotationIEAGOIEA1.11.1PRDX1,2,5 catalyze TXN reduced + H2O2 => TXN oxidized + 2H2OPRDX1,2,5 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>Reactome DB_ID: 294081hydrogen peroxide [ChEBI:16240]hydrogen peroxideChEBI16240Reactome DB_ID: 101926761UniProt:Q7ZUI4UniProtQ7ZUI42EQUAL105EQUALReactome DB_ID: 101926741Intra-chain Crosslink via L-cystine (cross-link) at 32 and 35 (in Homo sapiens)32EQUALL-cystine (cross-link)2EQUAL105EQUALReactome DB_ID: 293562PHYSIOL-LEFT-TO-RIGHTACTIVATIONConverted from EntitySet in ReactomeReactome DB_ID: 10260276PRDX1,2,5 [cytosol]Converted from EntitySet in Reactome. Each synonym is a name of a PhysicalEntity, and each XREF points to one PhysicalEntityprdx5 [cytosol]UniProtF1QCE3GO0008379GO molecular functionReactome Database ID Release 7510260277Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10260277Reactome Database ID Release 7510260279Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10260279ReactomeR-DRE-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-DRE-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. 282:22011-22inferred by electronic annotationIEAGOIEA1.11.1.7PRDX1 overoxidizesPRDX1 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>Reactome DB_ID: 294082Reactome DB_ID: 102602661PRDX1 dimer [cytosol]PRDX1 dimerReactome DB_ID: 102602642UniProt:A2AWE1prdx1UniProtA2AWE12EQUAL199EQUALReactome Database ID Release 7510260266Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10260266ReactomeR-DRE-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-DRE-3341319.1Reactome DB_ID: 102694501HOOS-C52-PRDX1 dimer [cytosol]HOOS-C52-PRDX1 dimerReactome DB_ID: 1026026412EQUAL199EQUALReactome DB_ID: 102694481L-cysteine sulfinic acid at 52 (in Homo sapiens)52EQUALL-cysteine sulfinic acid2EQUAL199EQUALReactome Database ID Release 7510269450Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10269450ReactomeR-DRE-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-DRE-5631882.1Reactome DB_ID: 293561PHYSIOL-LEFT-TO-RIGHTACTIVATIONReactome DB_ID: 10260266GO0004601GO molecular functionReactome Database ID Release 7510269451Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10269451Reactome Database ID Release 7510269453Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10269453ReactomeR-DRE-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-DRE-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 304:596-600inferred by electronic annotationIEAGOIEASESN1,2,3 bind overoxidized PRDX1SESN1,2,3 bind overoxidized PRDX1Sestrins 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 ReactomeReactome DB_ID: 102694691SESN1,2,3 [cytosol]Converted from EntitySet in Reactome. Each synonym is a name of a PhysicalEntity, and each XREF points to one PhysicalEntitysesn2 [cytosol]sesn1 [cytosol]UniProtA0F081UniProtU3JAG5Reactome DB_ID: 102694501Reactome DB_ID: 102694711SESN1,2,3:HOOS-C52-PRDX1 dimer [cytosol]SESN1,2,3:HOOS-C52-PRDX1 dimerConverted from EntitySet in ReactomeReactome DB_ID: 102694691Reactome DB_ID: 102694501Reactome Database ID Release 7510269471Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10269471ReactomeR-DRE-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-DRE-5631902.1Reactome Database ID Release 7510269473Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10269473ReactomeR-DRE-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-DRE-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. 32:455inferred by electronic annotationIEAGOIEA2.7.11.11p-AMPK phosphorylates TSC1:TSC2p-AMPK phosphorylates TSC1:TSC2This 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 DB_ID: 1135921ATP(4-) [ChEBI:30616]ATP(4-)Adenosine 5'-triphosphateatpATPChEBI30616Reactome DB_ID: 102002051TSC1:TSC2 [cytosol]TSC1:TSC2Reactome DB_ID: 102001891UniProt:A0A0G2KHX4tsc2UniProtA0A0G2KHX41EQUAL1807EQUALReactome DB_ID: 102002031UniProt:E7FEJ0tsc1bUniProtE7FEJ01EQUAL1164EQUALReactome Database ID Release 7510200205Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10200205ReactomeR-DRE-1651751Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-DRE-165175.1Reactome DB_ID: 293701ADP(3-) [ChEBI:456216]ADP(3-)ADP trianion5&apos;-O-[(phosphonatooxy)phosphinato]adenosineADPChEBI456216Reactome DB_ID: 102173621plasma membraneGO0005886TSC1:p-S1387-TSC2 [plasma membrane]TSC1:p-S1387-TSC2Reactome DB_ID: 102173601O-phospho-L-serine at 1387 (in Homo sapiens)1387EQUALO-phospho-L-serine [MOD:00046]1EQUAL1807EQUALReactome DB_ID: 1020020111EQUAL1164EQUALReactome Database ID Release 7510217362Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10217362ReactomeR-DRE-3818551Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-DRE-381855.1PHYSIOL-LEFT-TO-RIGHTACTIVATIONReactome DB_ID: 10217364p-AMPK heterotrimer:AMP [cytosol]p-AMPK heterotrimer:AMPReactome DB_ID: 765771adenosine 5'-monophosphate [ChEBI:16027]adenosine 5'-monophosphateChEBI16027Reactome DB_ID: 102082981p-AMPK heterotrimer [cytosol]p-AMPK heterotrimerConverted from EntitySet in ReactomeReactome DB_ID: 102082961p-AMPK alpha [cytosol]Converted from EntitySet in Reactome. Each synonym is a name of a PhysicalEntity, and each XREF points to one PhysicalEntityphospho-prkaa1 [cytosol]phospho-prkaa2 [cytosol]UniProtA5WUM0UniProtE7F9C4Converted from EntitySet in ReactomeReactome DB_ID: 102082741AMPK beta [cytosol]Converted from EntitySet in Reactome. Each synonym is a name of a PhysicalEntity, and each XREF points to one PhysicalEntityprkab1a [cytosol]PRKAB2 [cytosol]UniProtQ6DHM2UniProtE7F9H4Converted from EntitySet in ReactomeReactome DB_ID: 102082861AMPK gamma [cytosol]Converted from EntitySet in Reactome. Each synonym is a name of a PhysicalEntity, and each XREF points to one PhysicalEntityprkag3b [cytosol]prkag2a [cytosol]prkag1 [cytosol]UniProtF1QK10UniProtF1QJ49UniProtQ6PCS7Reactome Database ID Release 7510208298Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10208298ReactomeR-DRE-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-DRE-380934.1Reactome Database ID Release 7510217364Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10217364ReactomeR-DRE-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-DRE-380931.1GO0004679GO molecular functionReactome Database ID Release 7510217365Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10217365Reactome Database ID Release 7510217367Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10217367ReactomeR-DRE-3809271Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-DRE-380927.1Activated AMPK (phosphorylated on the alpha subunit and with AMP bound) phosphorylates TSC2 (also known as tuberin) on Ser-1387, thereby activating the GTPase activating protein (GAP) activity of the Tuberous Sclerosis Complex (TSC). The TSC tumor suppressor is a critical upstream inhibitor of the mTORC1 complex. TSC is a GTPase-activating protein that stimulates the intrinsic GTPase activity of the small G-protein Rheb. This inactivates Rheb by stimulating its GTPase activity. The GDP-bound form of Rheb looses the ability to activate the kinase activity of the mTORC1 complex (Sancak et al. 2007). Loss of TSC1 or TSC2 leads to hyperactivation of mTORC1. <br><br>Phosphorylation of TSC1 and TSC2 serves as an integration point for a wide variety of environmental signals that regulate mTORC1 (Sabatini 2006). Mitogen-activated kinases including Akt, Erk, and Rsk directly phosphorylate TSC2, leading to its inactivation by an unknown mechanism. Another Akt substrate, PRAS40, was recently shown to bind and inhibit the mTORC1 complex. Upon phosphorylation by Akt, PRAS40 no longer inhibits mTORC1 (Sancak et al. 2007; Vander Haar et al. 2007).17386266Pubmed2007PRAS40 is an insulin-regulated inhibitor of the mTORC1 protein kinaseSancak, YThoreen, CCPeterson, TRLindquist, RAKang, SASpooner, ECarr, SASabatini, DMMol Cell 25:903-1517277771Pubmed2007Insulin signalling to mTOR mediated by the Akt/PKB substrate PRAS40Vander Haar, ELee, SIBandhakavi, SGriffin, TJKim, DHNat Cell Biol 9:316-2314651849Pubmed2003TSC2 mediates cellular energy response to control cell growth and survivalInoki, KZhu, TGuan, KLCell 115:577-90inferred by electronic annotationIEAGOIEA3.6.5.43.6.5.33.6.5.23.6.5.1RHEB in mTORC1:RHEB:GTP hydrolyses GTPRHEB 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>Reactome DB_ID: 102002971lysosomal membraneGO0005765Active mTORC1 complex [lysosomal membrane]Active mTORC1 complexReactome DB_ID: 102002191RHEB:GTP [lysosomal membrane]RHEB:GTPReactome DB_ID: 102002151UniProt:Q08CD8rhebl1UniProtQ08CD81EQUAL181EQUALReactome DB_ID: 294381GTP [ChEBI:15996]GTPGuanosine 5'-triphosphateChEBI15996Reactome Database ID Release 7510200219Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10200219ReactomeR-DRE-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-DRE-165189.1Reactome DB_ID: 102002951mTORC1:Ragulator:RagA,B:GTP:RagC,D:GDP:SLC38A9 [lysosomal membrane]mTORC1:Ragulator:RagA,B:GTP:RagC,D:GDP:SLC38A9Reactome DB_ID: 102002351mTORC1 [cytosol]mTORC1Reactome DB_ID: 102002251UniProt:Q803V5mlst8UniProtQ803V51EQUAL326EQUALReactome DB_ID: 102002331UniProt:A0A0R4IFI0rptorUniProtA0A0R4IFI01EQUAL1335EQUALReactome DB_ID: 102002291UniProt:B0UX67mtorUniProtB0UX671EQUAL2549EQUALReactome Database ID Release 7510200235Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10200235ReactomeR-DRE-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-DRE-377400.1Reactome DB_ID: 102002931Ragulator:RagA,B:GTP:RagC,D:GDP:SLC38A9 [lysosomal membrane]Ragulator:RagA,B:GTP:RagC,D:GDP:SLC38A9Reactome DB_ID: 102002911Ragulator:RagA,B:GTP:RagC,D:GDP [lysosomal membrane]Ragulator:RagA,B:GTP:RagC,D:GDPReactome DB_ID: 102002891RagA,B:GTP:RagC,D:GDP [cytosol]RagA,B:GTP:RagC,D:GDPConverted from EntitySet in ReactomeReactome DB_ID: 102002731RRAGA, RRAGB:GTP [cytosol]Converted from EntitySet in Reactome. Each synonym is a name of a PhysicalEntity, and each XREF points to one PhysicalEntityConverted from EntitySet in ReactomeReactome DB_ID: 102002871RRAGC,RRAGD:GDP [cytosol]Converted from EntitySet in Reactome. Each synonym is a name of a PhysicalEntity, and each XREF points to one PhysicalEntityReactome Database ID Release 7510200289Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10200289ReactomeR-DRE-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-DRE-5653945.1Reactome DB_ID: 102002611Ragulator [lysosomal membrane]RagulatorReactome DB_ID: 102002551UniProt:Q0P3X8lamtor4UniProtQ0P3X81EQUAL99EQUALReactome DB_ID: 102002431UniProt:E7FBZ6lamtor1UniProtE7FBZ62EQUAL161EQUALReactome DB_ID: 102002471UniProt:Q6DEG4lamtor2UniProtQ6DEG41EQUAL125EQUALReactome DB_ID: 102002511UniProt:Q503S6lamtor3UniProtQ503S61EQUAL124EQUALReactome DB_ID: 102002591UniProt:E7FA90lamtor5UniProtE7FA901EQUAL91EQUALReactome Database ID Release 7510200261Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10200261ReactomeR-DRE-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-DRE-5653921.1Reactome Database ID Release 7510200291Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10200291ReactomeR-DRE-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-DRE-5653979.1Reactome DB_ID: 102002391UniProt:Q08BA4slc38a9UniProtQ08BA41EQUAL561EQUALReactome Database ID Release 7510200293Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10200293ReactomeR-DRE-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-DRE-8952725.1Reactome Database ID Release 7510200295Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10200295ReactomeR-DRE-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-DRE-5653972.1Reactome Database ID Release 7510200297Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10200297ReactomeR-DRE-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-DRE-165678.1Reactome DB_ID: 293721Reactome DB_ID: 102173761mTORC1:Ragulator:Rag:GNP:RHEB:GDP [lysosomal membrane]mTORC1:Ragulator:Rag:GNP:RHEB:GDPReactome DB_ID: 102002171RHEB:GDP [lysosomal membrane]RHEB:GDPReactome DB_ID: 1020021511EQUAL181EQUALReactome DB_ID: 294201GDP [ChEBI:17552]GDPGuanosine 5'-diphosphateGuanosine diphosphateChEBI17552Reactome Database ID Release 7510200217Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10200217ReactomeR-DRE-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-DRE-165191.1Reactome DB_ID: 102002951Reactome Database ID Release 7510217376Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10217376ReactomeR-DRE-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-DRE-5693447.1PHYSIOL-LEFT-TO-RIGHTACTIVATIONReactome DB_ID: 10200297GO0003924GO molecular functionReactome Database ID Release 7510217377Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10217377Reactome Database ID Release 7510217379Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10217379ReactomeR-DRE-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-DRE-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 13:1259-68inferred by electronic annotationIEAGOIEAACTIVATIONReactome Database ID Release 7510217380Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10217380Reactome DB_ID: 10217362SESN1,2,3 bind AMPKSESN1,2,3 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>Reactome DB_ID: 102173641Converted from EntitySet in ReactomeReactome DB_ID: 102694691Reactome DB_ID: 102694751SESN1,2,3:p-AMPK heterotrimer:AMP [cytosol]SESN1,2,3:p-AMPK heterotrimer:AMPReactome DB_ID: 102173641Converted from EntitySet in ReactomeReactome DB_ID: 102694691Reactome Database ID Release 7510269475Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10269475ReactomeR-DRE-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-DRE-5631939.1Reactome Database ID Release 7510269477Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10269477ReactomeR-DRE-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-DRE-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. 289:4083-94inferred by electronic annotationIEAGOIEAFormation of TSC1:TSC2 complexFormation of TSC1:TSC2 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>Reactome DB_ID: 1020018911EQUAL1807EQUALReactome DB_ID: 1020020111EQUAL1164EQUALReactome DB_ID: 102002051Reactome Database ID Release 7510200207Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10200207ReactomeR-DRE-1651791Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-DRE-165179.1A membrane-associated TSC1 (hamartin) binds TSC2 (tuberin) and recruits it to the plasma membrane where it can exert its function as a GAP (GTPase activating protein) for the small GTPase RHEB (Cai et al. 2006). 16636147Pubmed2006Activity 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. 173:279-8915589136Pubmed2004Signaling pathways: the benefits of good communicationFisher, TLWhite, MFCurr Biol 14:R1005-7inferred by electronic annotationIEAGOIEA2.7.11AKT phosphorylates TSC2, inhibiting itAKT 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>Reactome DB_ID: 1020018911EQUAL1807EQUALReactome DB_ID: 1135922Reactome DB_ID: 293702Reactome DB_ID: 102068371O-phospho-L-serine at 939 (in Homo sapiens)939EQUALO-phospho-L-threonine at 1462 (in Homo sapiens)1462EQUALO-phospho-L-threonine [MOD:00047]1EQUAL1807EQUALPHYSIOL-LEFT-TO-RIGHTACTIVATIONConverted from EntitySet in ReactomeReactome DB_ID: 10206769p-T,p-S-AKT [cytosol]Converted from EntitySet in Reactome. Each synonym is a name of a PhysicalEntity, and each XREF points to one PhysicalEntityphospho-akt2 [cytosol]phospho-akt2l [cytosol]UniProtQ8UUX0UniProtA0A0R4IY09GO0004674GO molecular functionReactome Database ID Release 7510206833Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10206833Reactome Database ID Release 7510206839Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10206839ReactomeR-DRE-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-DRE-198609.1GO0043491GO biological processAKT 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 10:151-62inferred by electronic annotationIEAGOIEAp-S939,T1462-TSC2 binding to 14-3-3 dimer is negatively regulated by DDIT4p-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 ReactomeReactome DB_ID: 10193962114-3-3 dimer [cytosol]Converted from EntitySet in Reactome. Each synonym is a name of a PhysicalEntity, and each XREF points to one PhysicalEntityReactome DB_ID: 102068371O-phospho-L-serine at 939 (in Homo sapiens)939EQUALO-phospho-L-threonine at 1462 (in Homo sapiens)1462EQUAL1EQUAL1807EQUALReactome DB_ID: 102695191p-S939,T1462-TSC2:14-3-3 dimer [cytosol]p-S939,T1462-TSC2:14-3-3 dimerConverted from EntitySet in ReactomeReactome DB_ID: 101939621Reactome DB_ID: 102068371O-phospho-L-serine at 939 (in Homo sapiens)939EQUALO-phospho-L-threonine at 1462 (in Homo sapiens)1462EQUAL1EQUAL1807EQUALReactome Database ID Release 7510269519Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10269519ReactomeR-DRE-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-DRE-5632727.1Reactome Database ID Release 7510269527Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10269527ReactomeR-DRE-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-DRE-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. 62:6475-80inferred by electronic annotationIEAGOIEAINHIBITIONReactome Database ID Release 7510269528Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10269528Reactome DB_ID: 10269525DDIT4:14-3-3 dimer [cytosol]DDIT4:14-3-3 dimerConverted from EntitySet in ReactomeReactome DB_ID: 101939621Reactome DB_ID: 102695231UniProt:Q7T346ddit4UniProtQ7T3461EQUAL232EQUALReactome Database ID Release 7510269525Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10269525ReactomeR-DRE-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-DRE-5632741.1DDIT4 binds 14-3-3 dimerDDIT4 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>Converted from EntitySet in ReactomeReactome DB_ID: 101939621Reactome DB_ID: 1026952311EQUAL232EQUALReactome DB_ID: 102695251Reactome Database ID Release 7510269530Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10269530ReactomeR-DRE-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-DRE-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. 22:239-51inferred by electronic annotationIEAGOIEA1.9.3.1Electron transfer from reduced cytochrome c to molecular oxygenElectron 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>Reactome DB_ID: 11352912mitochondrial matrixGO0005759Reactome DB_ID: 1135331dioxygen [ChEBI:15379]dioxygenChEBI15379Reactome DB_ID: 101994524mitochondrial inner membraneGO0005743Cytochrome c (reduced) [mitochondrial inner membrane]Cytochrome c (reduced)Reactome DB_ID: 33413171ferroheme [ChEBI:38573]ferrohemeferrohaemChEBI38573Reactome DB_ID: 101994501UniProt:Q6IQM2cycUniProtQ6IQM22EQUAL105EQUALReactome Database ID Release 7510199452Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10199452ReactomeR-DRE-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-DRE-352609.1Reactome DB_ID: 1639538mitochondrial intermembrane spaceGO0005758Reactome DB_ID: 101994544Cytochrome c (oxidised) [mitochondrial inner membrane]Cytochrome c (oxidised)Reactome DB_ID: 33413711ferriheme [ChEBI:38574]ferrihemeferrihaemChEBI38574Reactome DB_ID: 1019945012EQUAL105EQUALReactome Database ID Release 7510199454Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10199454ReactomeR-DRE-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-DRE-352607.1Reactome DB_ID: 1135212PHYSIOL-LEFT-TO-RIGHTACTIVATIONReactome DB_ID: 10199522Cytochrome c oxidase [mitochondrial inner membrane]Cytochrome c oxidaseReactome DB_ID: 101994941UniProt:F1RCH5UniProtF1RCH532EQUAL129EQUALReactome DB_ID: 101994981UniProt:Q9MIY8mt-co1UniProtQ9MIY81EQUAL513EQUALReactome DB_ID: 101994861Ghost homologue of COX6C(3-75) [mitochondrial inner membrane]Ghost homologue of COX6C(3-75)Reactome DB_ID: 101995201UniProt:Q6PBH5ndufa4UniProtQ6PBH51EQUAL81EQUALReactome DB_ID: 101995061UniProt:Q9MIY4mt-co3UniProtQ9MIY42EQUAL261EQUALReactome DB_ID: 101994901UniProt:Q4VBU7cox5aaUniProtQ4VBU742EQUAL150EQUALReactome DB_ID: 101994761UniProt:Q6PBP0cox7cUniProtQ6PBP017EQUAL63EQUALReactome DB_ID: 101995141UniProt:Q7SXI1cox7a2lUniProtQ7SXI156EQUAL114EQUALReactome DB_ID: 101994721UniProt:A0A2R8QKW1cox7bUniProtA0A2R8QKW125EQUAL80EQUALReactome DB_ID: 101995021UniProt:Q9MIY7mt-co2UniProtQ9MIY71EQUAL227EQUALReactome DB_ID: 101994801UniProt:A9C462cox6a1UniProtA9C46225EQUAL109EQUALReactome DB_ID: 101994841UniProt:Q7SXM1cox6b2UniProtQ7SXM12EQUAL86EQUALConverted from EntitySet in ReactomeReactome DB_ID: 101994681Homologues of COX8A [mitochondrial inner membrane]Converted from EntitySet in Reactome. Each synonym is a name of a PhysicalEntity, and each XREF points to one PhysicalEntitysi:dkey-85n7.8 [mitochondrial inner membrane]cox8b [mitochondrial inner membrane]cox8a [mitochondrial inner membrane]UniProtF8W4B6UniProtX1WER9UniProtE9QFA6Reactome DB_ID: 101995101UniProt:Q6TNV0cox4i1UniProtQ6TNV023EQUAL169EQUALReactome DB_ID: 101995161MT-CO2:CuA [mitochondrial inner membrane]MT-CO2:CuAReactome DB_ID: 1643001copper atom [ChEBI:28694]copper atomcuivreCucoppercuprumCopperKupfer29CucobreChEBI28694Reactome DB_ID: 1019950211EQUAL227EQUALReactome Database ID Release 7510199516Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10199516ReactomeR-DRE-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-DRE-164303.1Reactome Database ID Release 7510199522Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10199522ReactomeR-DRE-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-DRE-164316.1GO0004129GO molecular functionReactome Database ID Release 7510199523Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10199523Reactome Database ID Release 7510199573Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10199573ReactomeR-DRE-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-DRE-163214.1GO0006123GO biological processComplex 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:C1129-47inferred by electronic annotationIEAGOIEAACTIVATIONReactome Database ID Release 7510199575Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10199575Converted from EntitySet in ReactomeReactome DB_ID: 10199549COX11,14,16,18,20 [mitochondrial inner membrane]Converted from EntitySet in Reactome. Each synonym is a name of a PhysicalEntity, and each XREF points to one PhysicalEntityCOX14 [mitochondrial inner membrane]cox20 [mitochondrial inner membrane]cox11 [mitochondrial inner membrane]cox16 [mitochondrial inner membrane]cox18 [mitochondrial inner membrane]UniProtA8E7D3UniProtQ6DH88UniProtA3KNN8UniProtB8JHU3UniProtA9JTC7ACTIVATIONReactome Database ID Release 7510199574Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10199574Reactome DB_ID: 10199527UniProt:B7ZVA6cox19UniProtB7ZVA62EQUAL90EQUALACTIVATIONReactome Database ID Release 7510199576Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10199576Converted from EntitySet in ReactomeReactome DB_ID: 10199571COX ancilliary proteins [mitochondrial matrix]Converted from EntitySet in Reactome. Each synonym is a name of a PhysicalEntity, and each XREF points to one PhysicalEntitylrpprc [mitochondrial matrix]taco1 [mitochondrial matrix]sco2 [mitochondrial matrix]sco1 [mitochondrial matrix]surf1 [mitochondrial matrix]UniProtF5H8N4UniProtA0A0G2L877UniProtQ5RH02UniProtA0A2R8Q8I4UniProtF1QUE83.5.1.2glutamine + H2O => glutamate + NH4+ [GLS]glutamine + 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>Reactome DB_ID: 1135221L-glutamine zwitterion [ChEBI:58359]L-glutamine zwitterion(2S)-5-amino-2-ammonio-5-oxopentanoate146.14450C5H10N2O3NC(=O)CC[C@H]([NH3+])C([O-])=OL-glutamine(2S)-5-amino-2-azaniumyl-5-oxopentanoateInChI=1S/C5H10N2O3/c6-3(5(9)10)1-2-4(7)8/h3H,1-2,6H2,(H2,7,8)(H,9,10)/t3-/m0/s1ZDXPYRJPNDTMRX-VKHMYHEASA-NChEBI58359Reactome DB_ID: 1135211Reactome DB_ID: 1135521L-glutamate(1-) [ChEBI:29985]L-glutamate(1-)C5H8NO4WHUUTDBJXJRKMK-VKHMYHEASA-M(2S)-2-ammoniopentanedioate146.12136L-glutamatehydrogen L-glutamateInChI=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/s1L-glutamic acid, ion(1-)[NH3+][C@@H](CCC([O-])=O)C([O-])=OL-glutamic acid monoanionChEBI29985Reactome DB_ID: 1135611ammonium [ChEBI:28938]ammoniumChEBI28938PHYSIOL-LEFT-TO-RIGHTACTIVATIONConverted from EntitySet in ReactomeReactome DB_ID: 10189997GLS dimers [mitochondrial matrix]Converted from EntitySet in Reactome. Each synonym is a name of a PhysicalEntity, and each XREF points to one PhysicalEntityGO0004359GO molecular functionReactome Database ID Release 7510189998Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10189998Reactome Database ID Release 7510190000Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10190000ReactomeR-DRE-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-DRE-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 255:1031-5inferred by electronic annotationIEAGOIEAReactome Database ID Release 7510302953Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10302953ReactomeR-DRE-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-DRE-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 712inferred by electronic annotationIEAGOIEATP53 Regulates Transcription of Cell Death GenesTP53 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 Death Receptors and LigandsTP53 Regulates Transcription of Death Receptors and LigandsThis 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>IGFBP3 binds TMEM219IGFBP3 binds TMEM219This 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 DB_ID: 102837781UniProt:F1QNC7UniProtF1QNC739EQUAL240EQUALReactome DB_ID: 102174821extracellular regionGO0005576UniProt:Q66I28igfbp3UniProtQ66I2828EQUAL291EQUALReactome DB_ID: 102837801IGFBP3:TMEM219 [plasma membrane]IGFBP3:TMEM219Reactome DB_ID: 10283778139EQUAL240EQUALReactome DB_ID: 10217482128EQUAL291EQUALReactome Database ID Release 7510283780Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10283780ReactomeR-DRE-68000241Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-DRE-6800024.1Reactome Database ID Release 7510283782Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10283782ReactomeR-DRE-68000351Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-DRE-6800035.1IGFBP3 binds a cell death receptor TMEM219 (IGFBP-3R), a single-span transmembrane protein. Activated TMEM219 can trigger apoptosis, probably by directly binding to and activating caspase-8 (CASP8) (Ingermann et al. 2010). 20353938Pubmed2010Identification 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. 285:30233-46inferred by electronic annotationIEAGOIEAReactome Database ID Release 7510305657Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10305657ReactomeR-DRE-68032111Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-DRE-6803211.1Pro-apoptotic transcriptional targets of TP53 are 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).15289308Pubmed2004p53 upregulates death receptor 4 expression through an intronic p53 binding siteLiu, XiangguoYue, PingKhuri, Fadlo RSun, Shi-YongCancer Res. 64:5078-8314623878Pubmed2004Tumor 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. 279:4093-1019326928Pubmed1997KILLER/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. 17:141-311382926Pubmed2001Evidence that the death receptor DR4 is a DNA damage-inducible, p53-regulated geneGuan, BYue, PClayman, G LSun, S YJ. Cell. Physiol. 188:98-10523365256Pubmed2013ASPP1/2 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. 33:2205-1610777207Pubmed2000Wild-type p53 transactivates the KILLER/DR5 gene through an intronic sequence-specific DNA-binding siteTakimoto, Rel-Deiry, WSOncogene 19:1735-4316230375Pubmed2005Decoy receptor 2 (DcR2) is a p53 target gene and regulates chemosensitivityLiu, XiangguoYue, PingKhuri, Fadlo RSun, Shi-YongCancer Res. 65:9169-757566179Pubmed1995Induction of the growth inhibitor IGF-binding protein 3 by p53Buckbinder, LTalbott, RVelasco-Miguel, STakenaka, IFaha, BSeizinger, B RKley, NNature 377:646-919615968Pubmed2009Active 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. 387:399-404inferred by electronic annotationIEAGOIEATP53 Regulates Transcription of Genes Involved in Cytochrome C ReleaseTP53 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>STEAP3 binds BNIP3LSTEAP3 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>Reactome DB_ID: 102847841mitochondrial outer membraneGO0005741UniProt:Q5VK49bnip3laUniProtQ5VK491EQUAL219EQUALReactome DB_ID: 102290811endosome membraneGO0010008UniProt:E7F9Y0steap3UniProtE7F9Y01EQUAL488EQUALReactome DB_ID: 102847861STEAP3:BNIP3L [mitochondrial outer membrane]STEAP3:BNIP3LReactome DB_ID: 1028478411EQUAL219EQUALReactome DB_ID: 1022908111EQUAL488EQUALReactome Database ID Release 7510284786Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10284786ReactomeR-DRE-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-DRE-6801198.1Reactome Database ID Release 7510284788Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10284788ReactomeR-DRE-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-DRE-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. 100:2284-9inferred by electronic annotationIEAGOIEATRIAP1 binds PRELID1, PRELID3ATRIAP1 binds PRELID1, PRELID3AThis 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 DB_ID: 102847921UniProt:F1Q6Y0triap1UniProtF1Q6Y01EQUAL76EQUALConverted from EntitySet in ReactomeReactome DB_ID: 102848021PRELID1, PRELID3A [mitochondrial intermembrane space]Converted from EntitySet in Reactome. Each synonym is a name of a PhysicalEntity, and each XREF points to one PhysicalEntityprelid1a [mitochondrial intermembrane space]UniProtQ7T388Reactome DB_ID: 102848041TRIAP1:PRELID1, PRELID3A [mitochondrial intermembrane space]TRIAP1:PRELID1, PRELID3AReactome DB_ID: 1028479211EQUAL76EQUALConverted from EntitySet in ReactomeReactome DB_ID: 102848021Reactome Database ID Release 7510284804Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10284804ReactomeR-DRE-68012351Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-DRE-6801235.1Reactome Database ID Release 7510284806Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10284806ReactomeR-DRE-68012421Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-DRE-6801242.1In the mitochondrial intermembrane space, TP53-regulated inhibitor of apoptosis 1 (TRIAP1) forms a complex with mitochondrial PRELI domain-containing protein 1 (PRELID1, PRELI) (Potting et al. 2013). TRIAP1 is also proposed to form a complex with PRELI domain containing protein 3A (PRELID3A) (Miliara et al. 2015). 23931759Pubmed2013TRIAP1/PRELI complexes prevent apoptosis by mediating intramitochondrial transport of phosphatidic acidPotting, ChristophTatsuta, TakashiKönig, TimHaag, MathiasWai, TimothyAaltonen, Mari JLanger, ThomasCell Metab. 18:287-9526071602Pubmed2015Structural insight into the TRIAP1/PRELI-like domain family of mitochondrial phospholipid transfer complexesMiliara, XeniGarnett, James ATatsuta, TakashiAbid Ali, FerdosBaldie, HeatherPérez-Dorado, InmaculadaSimpson, PeterYague, ErnestoLanger, ThomasMatthews, StephenEMBO Rep. 16:824-35inferred by electronic annotationIEAGOIEATRIAP1:PRELID1, PRELID3A transports PA from the outer to the inner mitochondrial membraneTRIAP1:PRELID1, PRELID3A transports PA from the outer to the inner mitochondrial membraneThis 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 DB_ID: 15005901phosphatidic acid [ChEBI:16337]phosphatidic acidChEBI16337Reactome DB_ID: 15241011PHYSIOL-LEFT-TO-RIGHTACTIVATIONReactome DB_ID: 10284804GO0005319GO molecular functionReactome Database ID Release 7510284807Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10284807Reactome Database ID Release 7510284809Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10284809ReactomeR-DRE-68012501Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-DRE-6801250.1The complex of TP53-regulated inhibitor of apoptosis 1 (TRIAP1) and mitochondrial PRELI domain-containing protein 1 PRELID1 (TRIAP1:PRELID1) facilitates transport of phosphatidic acid (PA) from the outer mitochondrial membrane to the inner mitochondrial membrane. At the inner mitochondrial membrane, the PA is used for the synthesis of cardiolipin (CL). CL prevents the release of cytochrome C from mitochondria, thus playing an anti-apoptotic role (Potting et al. 2013). The complex between TRIAP1 and PRELI domain containing protein 3A (PRELID3A) is suggested to perform the same PA transport activity (Miliara et al. 2015)inferred by electronic annotationIEAGOIEAReactome Database ID Release 7510305667Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10305667ReactomeR-DRE-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-DRE-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 6:597-60911463392Pubmed2001PUMA, 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 64:3022-9inferred by electronic annotationIEAGOIEATP53 Regulates Transcription of Caspase Activators and CaspasesTP53 Regulates Transcription of Caspase Activators and CaspasesThis 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>2.7.11ATM phosphorylates PIDD1ATM phosphorylates PIDD1This 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 ReactomeReactome DB_ID: 102847181nucleoplasmGO0005654Homologues of PIDD1 [nucleoplasm]Converted from EntitySet in Reactome. Each synonym is a name of a PhysicalEntity, and each XREF points to one PhysicalEntitymfhas1 [nucleoplasm]pidd1 [nucleoplasm]mfhas1 [nucleoplasm]UniProtA0A2R8RUG7UniProtE9QFQ1UniProtF1QVP4Reactome DB_ID: 293581Converted from EntitySet in ReactomeReactome DB_ID: 102847291Homologues of p-T788-PIDD1 [nucleoplasm]Converted from EntitySet in Reactome. Each synonym is a name of a PhysicalEntity, and each XREF points to one PhysicalEntityphospho-mfhas1 [nucleoplasm]phospho-pidd1 [nucleoplasm]phospho-mfhas1 [nucleoplasm]Reactome DB_ID: 1135821PHYSIOL-LEFT-TO-RIGHTACTIVATIONReactome DB_ID: 10189374UniProt:F1QJB6atmUniProtF1QJB6O-phospho-L-serine at 1981 (in Homo sapiens)1981EQUALN6-acetyl-L-lysine at 3016 (in Homo sapiens)3016EQUALN6-acetyl-L-lysine [MOD:00064]1EQUAL3056EQUALReactome Database ID Release 7510212287Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10212287Reactome Database ID Release 7510284731Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10284731ReactomeR-DRE-68004901Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-DRE-6800490.1In response to DNA damage, activated ATM phosphorylates PIDD1 at threonine residue T788, a prerequisite for the subsequent interaction with CRADD (RAIDD) (Ando et al. 2012).22854598Pubmed2012PIDD death-domain phosphorylation by ATM controls prodeath versus prosurvival PIDDosome signalingAndo, KKernan, Jennifer LLiu, Peter HSanda, TakaomiLogette, EmmanuelleTschopp, JürgLook, A ThomasWang, JianlongBouchier-Hayes, LisaSidi, SamuelMol. Cell 47:681-93inferred by electronic annotationIEAGOIEAPIDD1 translocates to the cytosolPIDD1 translocates to the cytosolThis 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 ReactomeReactome DB_ID: 102847291Converted from EntitySet in ReactomeReactome DB_ID: 102847391Homologues of p-T788-PIDD1 [cytosol]Converted from EntitySet in Reactome. Each synonym is a name of a PhysicalEntity, and each XREF points to one PhysicalEntityphospho-mfhas1 [cytosol]phospho-pidd1 [cytosol]phospho-mfhas1 [cytosol]Reactome Database ID Release 7510284741Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10284741ReactomeR-DRE-68007931Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-DRE-6800793.1PIDD1 can localize both to the nucleus and to the cytoplasm. It is not known whether ATM-mediated phosphorylation regulates PIDD1 localization, but PIDDosome formation and caspase-2 activation is thought to be predominantly cytoplasmic (Ando et al. 2012).inferred by electronic annotationIEAGOIEAPIDD1 associates with CRADDPIDD1 associates with CRADDThis 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 ReactomeReactome DB_ID: 102847395Reactome DB_ID: 102847457UniProt:Q5XJP2craddUniProtQ5XJP21EQUAL199EQUALReactome DB_ID: 102847471PIDDosome [cytosol]PIDDosomeConverted from EntitySet in ReactomeReactome DB_ID: 102847395Reactome DB_ID: 1028474571EQUAL199EQUALReactome Database ID Release 7510284747Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10284747ReactomeR-DRE-68007821Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-DRE-6800782.1Reactome Database ID Release 7510284749Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10284749ReactomeR-DRE-68007941Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-DRE-6800794.1PIDD1 phosphorylated by ATM at threonine residue T788 associates with CRADD (RAIDD), forming a multisubunit structure known as the PIDDosome (Tinel and Tschopp 2004, Ando et al. 2012). The PIDDosome consists of 5 molecules of PIDD1 and 5-7 molecules of CRADD (Nematollahi et al. 2015).25528640Pubmed2015Flexible stoichiometry and asymmetry of the PIDDosome core complex by heteronuclear NMR spectroscopy and mass spectrometryNematollahi, Lily AGarza-Garcia, AcelyBechara, ChérineEsposito, DiegoMorgner, NinaRobinson, CVDriscoll, Paul CJ. Mol. Biol. 427:737-5215073321Pubmed2004The PIDDosome, a protein complex implicated in activation of caspase-2 in response to genotoxic stressTinel, AntoineTschopp, JürgScience 304:843-6inferred by electronic annotationIEAGOIEAThe PIDDosome binds CASP2The PIDDosome binds CASP2This 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 DB_ID: 102847471Reactome DB_ID: 102102001UniProt:A0A288CG41casp2UniProtA0A288CG412EQUAL452EQUALReactome DB_ID: 102847511PIDDosome:CASP2(2-452) [cytosol]PIDDosome:CASP2(2-452)Reactome DB_ID: 102847471Reactome DB_ID: 1021020012EQUAL452EQUALReactome Database ID Release 7510284751Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10284751ReactomeR-DRE-68008031Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-DRE-6800803.1Reactome Database ID Release 7510284756Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10284756ReactomeR-DRE-68007981Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-DRE-6800798.1PIDD1, when phosphorylated by ATM at threonine residue T788, associates with CRADD (RAIDD), forming a multisubunit structure known as the PIDDosome (Tinel and Tschopp 2004, Ando et al. 2012). The PIDDosome binds procaspase-2 (CASP2), with CASP2 directly interacting with the CRADD subunit (Tinel and Tschopp 2004).inferred by electronic annotationIEAGOIEAThe PIDDosome activates CASP2The PIDDosome activates CASP2This 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 DB_ID: 102847511Reactome DB_ID: 102102061170EQUAL325EQUALReactome DB_ID: 102102041348EQUAL452EQUALReactome DB_ID: 102847471PHYSIOL-LEFT-TO-RIGHTACTIVATIONReactome DB_ID: 10284751GO0097153GO molecular functionReactome Database ID Release 7510284752Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10284752Reactome Database ID Release 7510284754Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10284754ReactomeR-DRE-68007971Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-DRE-6800797.1The PIDDosome promotes activation of CASP2 (caspase-2) by proteolytic cleavage, triggering apoptosis (Tinel and Tschopp 2004). The PIDDosome may also participate in the proteolytic activation of CASP3 and CASP7 (Berube et al. 2005).16183742Pubmed2005Apoptosis caused by p53-induced protein with death domain (PIDD) depends on the death adapter protein RAIDDBerube, ChristinaBoucher, Louis-MartinMa, WeiliWakeham, AndrewSalmena, LeonardoHakem, RazqallahYeh, WCMak, Tak WBenchimol, SamuelProc. Natl. Acad. Sci. U.S.A. 102:14314-20inferred by electronic annotationIEAGOIEAReactome Database ID Release 7510305665Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10305665ReactomeR-DRE-68032071Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-DRE-6803207.1TP53 (p53) transcriptionally regulates cytosolic caspase activators, such as APAF1, PIDD1, and NLRC4, and caspases themselves, such as CASP1, CASP6 and CASP10. These caspases and their activators are involved either in the intrinsic apoptosis pathway or in the extrinsic apoptosis pathway triggerred by death receptors or the inflammation-related cell death pyroptosis (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).14688482Pubmed2003Caspase 10 levels are increased following DNA damage in a p53-dependent mannerRikhof, BartCorn, Paul GEl-Deiry, Wafik SCancer Biol. Ther. 2:707-1217284521Pubmed2007Caspase-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. 99:9492-715580302Pubmed2005Caspase-1 activator Ipaf is a p53-inducible gene involved in apoptosisSadasivam, SGupta, SRadha, VegesnaBatta, KiranKundu, Tapas KSwarup, GhanshyamOncogene 24:627-3610973264Pubmed2000Pidd, 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. 61:6660-4inferred by electronic annotationIEAGOIEATP53 regulates transcription of several additional cell death genes whose specific roles in p53-dependent apoptosis remain uncertainTP53 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>TP53I3 dimerizesTP53I3 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>Converted from EntitySet in ReactomeReactome DB_ID: 102836672Homologues of TP53I3 [cytosol]Converted from EntitySet in Reactome. Each synonym is a name of a PhysicalEntity, and each XREF points to one PhysicalEntitytp53i3 [cytosol]tp53i3 [cytosol]UniProtA0A286Y901UniProtA0A286YBD8Reactome DB_ID: 102836691TP53I3 Dimer [cytosol]TP53I3 DimerConverted from EntitySet in ReactomeReactome DB_ID: 102836672Reactome Database ID Release 7510283669Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10283669ReactomeR-DRE-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-DRE-6799448.1Reactome Database ID Release 7510283671Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10283671ReactomeR-DRE-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-DRE-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. 284:17194-205inferred by electronic annotationIEAGOIEA1.6.5.5TP53I3 oxidoreductase generates unstable semiquinonesTP53I3 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>Reactome DB_ID: 293641Reactome DB_ID: 679972521,2-Naphthoquinone [ChEBI:34055]1,2-Naphthoquinone1,2-NaphthalenedioneChEBI34055Reactome DB_ID: 701061Reactome DB_ID: 67997262semiquinone [ChEBI:15817]semiquinoneSemiquinone radicalSemidionesemiquinonesChEBI15817Reactome DB_ID: 293661PHYSIOL-LEFT-TO-RIGHTACTIVATIONReactome DB_ID: 10283669GO0003960GO molecular functionReactome Database ID Release 7510283721Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10283721Reactome Database ID Release 7510283723Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10283723ReactomeR-DRE-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-DRE-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).inferred by electronic annotationIEAGOIEARABGGTA binds RABGGTBRABGGTA binds RABGGTBThis 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 DB_ID: 102847681UniProt:Q4V946rabggtbUniProtQ4V9462EQUAL331EQUALReactome DB_ID: 102847641UniProt:F1QJ77rabggtaUniProtF1QJ771EQUAL567EQUALReactome DB_ID: 102847701RGGT [plasma membrane]RGGTReactome DB_ID: 1028476812EQUAL331EQUALReactome DB_ID: 1028476411EQUAL567EQUALReactome Database ID Release 7510284770Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10284770ReactomeR-DRE-68011051Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-DRE-6801105.1Reactome Database ID Release 7510284772Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10284772ReactomeR-DRE-68011011Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-DRE-6801101.1RABGGTA associates with RABGGTB to form RAB geranylgeranyl transferase (RGGT or RAB GGTase). This was initially shown using proteins purified from rat brain (Seabra et al. 1992), but the complex is evolutionarily conserved in human cells (Baron and Seabra 2008).1321151Pubmed1992Rab geranylgeranyl transferase. A multisubunit enzyme that prenylates GTP-binding proteins terminating in Cys-X-Cys or Cys-CysSeabra, M CGoldstein, J LSudhof, T CBrown, M SJ. Biol. Chem. 267:14497-50318532927Pubmed2008Rab geranylgeranylation occurs preferentially via the pre-formed REP-RGGT complex and is regulated by geranylgeranyl pyrophosphateBaron, Rudi ASeabra, Miguel CBiochem. J. 415:67-75inferred by electronic annotationIEAGOIEACHM binds RGGTCHM binds RGGTThis 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 DB_ID: 102847701Reactome DB_ID: 102847761UniProt:F1Q9R8chmUniProtF1Q9R81EQUAL653EQUALReactome DB_ID: 102847781RGGT:CHM [plasma membrane]RGGT:CHMReactome DB_ID: 102847701Reactome DB_ID: 1028477611EQUAL653EQUALReactome Database ID Release 7510284778Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10284778ReactomeR-DRE-68011111Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-DRE-6801111.1Reactome Database ID Release 7510284780Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10284780ReactomeR-DRE-68011091Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-DRE-6801109.1RAB escort protein CHM (REP1) binds the RAB geranylgeranyl transferase complex, RGGT, composed of RABGGTA and RABGGTB (Baron and Seabra 2008). The interaction between CHM and the RGGT complex is enhanced by the presence of phosphoisoprenoids (Thoma et al. 2001). The complex of RGGT and CHM catalyzes geranylgeranylation of small GTPases RAB1A, RAB3A and RAB5A, which is needed for the membrane localization of RABs (Farnsworth et al. 1994). RAB geranylgeranyl transferase can play an anti-apoptotic role, through an unknown mechanism (Lackner et al. 2005). RAB5A, the substrate of RGGT:CHM complex, was shown to positively regulate formation of autophagosomes (Li et al. 2013). 15837622Pubmed2005Chemical genetics identifies Rab geranylgeranyl transferase as an apoptotic target of farnesyl transferase inhibitorsLackner, Mark RKindt, Rachel MCarroll, Pamela MBrown, KatherineCancilla, Michael RChen, Changyoude Silva, HeshaniFranke, YvonneGuan, BoHeuer, TimHung, TakKeegan, KevinLee, Jae MoonManne, VeeraswamyO'Brien, CarolParry, DiannePerez-Villar, Juan JReddy, Rajashekar KXiao, HongZhan, HangjunCockett, MarkPlowman, GregFitzgerald, KevinCosta, MichaelRoss-Macdonald, PetraCancer Cell 7:325-3611675392Pubmed2001Phosphoisoprenoids modulate association of Rab geranylgeranyltransferase with REP-1Thomä, N HIakovenko, AGoody, R SAlexandrov, KJ. Biol. Chem. 276:48637-437991565Pubmed1994Rab geranylgeranyl transferase catalyzes the geranylgeranylation of adjacent cysteines in the small GTPases Rab1A, Rab3A, and Rab5AFarnsworth, C CSeabra, M CEricsson, L HGelb, M HGlomset, J AProc. Natl. Acad. Sci. U.S.A. 91:11963-723182941Pubmed2013A novel ER-localized transmembrane protein, EMC6, interacts with RAB5A and regulates cell autophagyLi, YanjunZhao, YuanboHu, JiaXiao, JuanQu, LiujingWang, ZhendaMa, DalongChen, YingyuAutophagy 9:150-63inferred by electronic annotationIEAGOIEAReactome Database ID Release 7510305651Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10305651ReactomeR-DRE-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-DRE-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. 14:704-18inferred by electronic annotationIEAGOIEAReactome Database ID Release 7510305653Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10305653ReactomeR-DRE-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-DRE-5633008.1GO0042981GO biological processThe 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:e64517349958Pubmed2007DYRK2 is targeted to the nucleus and controls p53 via Ser46 phosphorylation in the apoptotic response to DNA damageTaira, NaoeNihira, KeishiYamaguchi, TomokoMiki, YoshioYoshida, KiyotsuguMol. Cell 25:725-3818431400Pubmed2008Transcriptional 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 14:359-7016135520Pubmed2005Role of p73 in regulating human caspase-1 gene transcription induced by interferon-{gamma} and cisplatinJain, NishantGupta, SSudhakar, ChRadha, VegesnaSwarup, GhanshyamJ. Biol. Chem. 280:36664-7315797384Pubmed2005Perp 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. 9:702-1226122615Pubmed2015p53 in survival, death and metabolic health: a lifeguard with a licence to killKruiswijk, FloreLabuschagne, Christiaan FVousden, Karen HNat. Rev. Mol. Cell Biol. 16:393-405inferred by electronic annotationIEAGOIEATP53 Regulates Transcription of Cell Cycle GenesTP53 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 ArrestTP53 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>Inactivation of Cyclin A:Cdk2 complexes by p27/p21Inactivation 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>Converted from EntitySet in ReactomeReactome DB_ID: 101892561CDKN1A,CDKN1B,(CDKN1C) [nucleoplasm]Converted from EntitySet in Reactome. Each synonym is a name of a PhysicalEntity, and each XREF points to one PhysicalEntitycdkn1a [nucleoplasm]cdkn1bb [nucleoplasm]UniProtA5WWG2UniProtQ90YX4Reactome DB_ID: 102023501CCNA:CDK2 [nucleoplasm]CCNA:CDK2Converted from EntitySet in ReactomeReactome DB_ID: 101888041CCNA [nucleoplasm]Converted from EntitySet in Reactome. Each synonym is a name of a PhysicalEntity, and each XREF points to one PhysicalEntityReactome DB_ID: 101887471UniProt:Q7ZWB1cdk2UniProtQ7ZWB11EQUAL298EQUALReactome Database ID Release 7510202350Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10202350ReactomeR-DRE-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-DRE-141608.1Reactome DB_ID: 102043651Cyclin A:Cdk2:p21/p27 complex [nucleoplasm]Cyclin A:Cdk2:p21/p27 complexConverted from EntitySet in ReactomeReactome DB_ID: 101892561Reactome DB_ID: 102023501Reactome Database ID Release 7510204365Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10204365ReactomeR-DRE-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-DRE-187926.1PHYSIOL-LEFT-TO-RIGHTACTIVATIONConverted from EntitySet in ReactomeReactome DB_ID: 10189256GO0004861GO molecular functionReactome Database ID Release 7510189277Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10189277Reactome Database ID Release 7510204372Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10204372ReactomeR-DRE-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-DRE-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 13:1181-9inferred by electronic annotationIEAGOIEAInactivation of Cyclin E:Cdk2 complexes by p27/p21Inactivation of Cyclin E: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>Reactome DB_ID: 101891301CCNE:CDK2 [nucleoplasm]CCNE:CDK2Converted from EntitySet in ReactomeReactome DB_ID: 101891281Cyclin E [nucleoplasm]Converted from EntitySet in Reactome. Each synonym is a name of a PhysicalEntity, and each XREF points to one PhysicalEntityReactome DB_ID: 1018874711EQUAL298EQUALReactome Database ID Release 7510189130Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10189130ReactomeR-DRE-683741Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-DRE-68374.1Converted from EntitySet in ReactomeReactome DB_ID: 101892561Reactome DB_ID: 101892761Cyclin E:CDK2:CDKN1A,CDKN1B [nucleoplasm]Cyclin E:CDK2:CDKN1A,CDKN1BReactome DB_ID: 101891301Converted from EntitySet in ReactomeReactome DB_ID: 101892561Reactome Database ID Release 7510189276Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10189276ReactomeR-DRE-683761Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-DRE-68376.1PHYSIOL-LEFT-TO-RIGHTACTIVATIONConverted from EntitySet in ReactomeReactome DB_ID: 10189256Reactome Database ID Release 7510189279Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10189279ReactomeR-DRE-695621Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-DRE-69562.1During 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 (see Guardavaccaro and Pagano, 2006). The efficient recognition and ubiquitination of p27 by the SCF (Skp2) complex requires the formation of a trimeric complex containing p27 and cyclin E/A:Cdk2.16262255Pubmed2005Ubiquitination of p21Cip1/WAF1 by SCFSkp2: substrate requirement and ubiquitination site selectionWang, WNacusi, LSheaff, RJLiu, XBiochemistry 44:14553-6416600864Pubmed2006Stabilizers and destabilizers controlling cell cycle oscillatorsGuardavaccaro, DPagano, MicheleMol Cell 22:1-4inferred by electronic annotationIEAGOIEAE2F7 forms homodimersE2F7 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>Reactome DB_ID: 102978682UniProt:Q5RIX9e2f7UniProtQ5RIX91EQUAL911EQUALReactome DB_ID: 102978701E2F7 homodimer [nucleoplasm]E2F7 homodimerReactome DB_ID: 1029786821EQUAL911EQUALReactome Database ID Release 7510297870Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10297870ReactomeR-DRE-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-DRE-8953000.1Reactome Database ID Release 7510297872Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10297872ReactomeR-DRE-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-DRE-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 23:5138-50inferred by electronic annotationIEAGOIEAE2F7 binds E2F8E2F7 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>Reactome DB_ID: 1029786811EQUAL911EQUALReactome DB_ID: 102978761UniProt:F1QZ88e2f8UniProtF1QZ881EQUAL867EQUALReactome DB_ID: 102978781E2F7:E2F8 [nucleoplasm]E2F7:E2F8Reactome DB_ID: 1029786811EQUAL911EQUALReactome DB_ID: 1029787611EQUAL867EQUALReactome Database ID Release 7510297878Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10297878ReactomeR-DRE-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-DRE-8953017.1Reactome Database ID Release 7510297880Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10297880ReactomeR-DRE-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-DRE-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. 9:252-9inferred by electronic annotationIEAGOIEAE2F8 forms homodimersE2F8 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>Reactome DB_ID: 1029787621EQUAL867EQUALReactome DB_ID: 102978821E2F8 homodimer [nucleoplasm]E2F8 homodimerReactome DB_ID: 1029787621EQUAL867EQUALReactome Database ID Release 7510297882Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10297882ReactomeR-DRE-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-DRE-8953035.1Reactome Database ID Release 7510297884Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10297884ReactomeR-DRE-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-DRE-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. 280:18211-20inferred by electronic annotationIEAGOIEAReactome Database ID Release 7510302867Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10302867ReactomeR-DRE-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-DRE-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 17:853-65inferred by electronic annotationIEAGOIEATP53 Regulates Transcription of Genes Involved in G2 Cell Cycle ArrestTP53 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>GADD45A binds AURKAGADD45A 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>Reactome DB_ID: 102790361UniProt:F1R8Z0gadd45aaUniProtF1R8Z01EQUAL165EQUALReactome DB_ID: 102795621UniProt:F1QEM3aurkaUniProtF1QEM31EQUAL403EQUALReactome DB_ID: 102795641GADD45A:AURKA [nucleoplasm]GADD45A:AURKAReactome DB_ID: 1027903611EQUAL165EQUALReactome DB_ID: 1027956211EQUAL403EQUALReactome Database ID Release 7510279564Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10279564ReactomeR-DRE-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-DRE-6791236.1Reactome Database ID Release 7510279566Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10279566ReactomeR-DRE-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-DRE-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. 285:22196-201inferred by electronic annotationIEAGOIEAGADD45A binds PCNAGADD45A 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>Reactome DB_ID: 1027903611EQUAL165EQUALReactome DB_ID: 101890311PCNA homotrimer [nucleoplasm]PCNA homotrimerReactome DB_ID: 101890293UniProt:Q9PTP1pcnaUniProtQ9PTP11EQUAL261EQUALReactome Database ID Release 7510189031Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10189031ReactomeR-DRE-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-DRE-68440.1Reactome DB_ID: 102790381GADD45A:PCNA [nucleoplasm]GADD45A:PCNAReactome DB_ID: 1027903611EQUAL165EQUALReactome DB_ID: 101890311Reactome Database ID Release 7510279038Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10279038ReactomeR-DRE-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-DRE-6791115.1Reactome Database ID Release 7510279040Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10279040ReactomeR-DRE-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-DRE-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 266:1376-80inferred by electronic annotationIEAGOIEASFN dimerizesSFN 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>Converted from EntitySet in ReactomeReactome DB_ID: 101939302Homologues of SFN [cytosol]Converted from EntitySet in Reactome. Each synonym is a name of a PhysicalEntity, and each XREF points to one PhysicalEntityywhaqa [cytosol]ywhaqb [cytosol]UniProtQ7ZUM0UniProtQ803M8Reactome DB_ID: 101939321SFN dimer [cytosol]SFN dimerConverted from EntitySet in ReactomeReactome DB_ID: 101939302Reactome Database ID Release 7510193932Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10193932ReactomeR-DRE-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-DRE-2262716.1Reactome Database ID Release 7510285044Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10285044ReactomeR-DRE-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-DRE-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 5:2920-6inferred by electronic annotationIEAGOIEASFN dimer binds CDK1 and CCNB1SFN dimer binds CDK1 and CCNB1This 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 DB_ID: 101939321Reactome DB_ID: 102850381CCNB1:CDK1 [cytosol]CCNB1:CDK1Reactome DB_ID: 102015621UniProt:Q7T3L7cdk1UniProtQ7T3L71EQUAL297EQUALReactome DB_ID: 102015171UniProt:Q7ZU21ccnb1UniProtQ7ZU211EQUAL433EQUALReactome Database ID Release 7510285038Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10285038ReactomeR-DRE-68038761Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-DRE-6803876.1Reactome DB_ID: 102850401SFN Dimer:CCNB1:CDK1 [cytosol]SFN Dimer:CCNB1:CDK1Reactome DB_ID: 101939321Reactome DB_ID: 102850381Reactome Database ID Release 7510285040Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10285040ReactomeR-DRE-68038781Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-DRE-6803878.1Reactome Database ID Release 7510285042Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10285042ReactomeR-DRE-68038751Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-DRE-6803875.1SFN (14-3-3-sigma) dimer binds the complex of CCNB1 (cyclin B1) and CDK1 (Cdc2) in the cytosol and prevents the translocation of the CCNB1:CDK1 complex into the nucleus. This induces G2 cell cycle arrest as nuclear localization of the CCNB1:CDK1 complex is necessary for phosphorylation of nuclear target proteins that are needed for the G2/M transition (Chan et al. 1999).10524633Pubmed199914-3-3Sigma is required to prevent mitotic catastrophe after DNA damageChan, T AHermeking, HLengauer, CKinzler, K WVogelstein, BNature 401:616-20inferred by electronic annotationIEAGOIEASFN dimer binds BAXSFN dimer binds BAXThis 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 DB_ID: 101939321Reactome DB_ID: 101970481UniProt:I3ITC2baxaUniProtI3ITC21EQUAL192EQUALReactome DB_ID: 102850461SFN Dimer:BAX [cytosol]SFN Dimer:BAXReactome DB_ID: 101939321Reactome DB_ID: 1019704811EQUAL192EQUALReactome Database ID Release 7510285046Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10285046ReactomeR-DRE-68038941Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-DRE-6803894.1Reactome Database ID Release 7510285048Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10285048ReactomeR-DRE-68038921Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-DRE-6803892.1SFN (14-3-3-sigma) dimer forms a complex with BAX. Binding of SFN to BAX prevents BAX translocation from cytosol to mitochondria, thus inhibiting cytochrome C release and apoptosis. SFN therefore promotes G2 cell cycle arrest while simultaneously preventing apoptosis (Samuel et al. 2001).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. 276:45201-6inferred by electronic annotationIEAGOIEAReactome Database ID Release 7510305635Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10305635ReactomeR-DRE-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-DRE-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).24096481Pubmed2014p53-dependent gene repression through p21 is mediated by recruitment of E2F4 repression complexesBenson, E KMungamuri, S KAttie, OKracikova, MSachidanandam, RManfredi, James JAaronson, Stuart AOncogene 33:3959-699659898Pubmed199714-3-3 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 16:725-36inferred by electronic annotationIEAGOIEATP53 regulates transcription of additional cell cycle genes whose exact role in the p53 pathway remain uncertainTP53 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>BTG2 binds CCR4-NOT complexBTG2 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>Reactome DB_ID: 102223731CCR4-NOT Complex [cytosol]CCR4-NOT ComplexConverted from EntitySet in ReactomeReactome DB_ID: 102223711CNOT7 or CNOT8 [cytosol]Converted from EntitySet in Reactome. Each synonym is a name of a PhysicalEntity, and each XREF points to one PhysicalEntitycnot7 [cytosol]cnot8 [cytosol]UniProtQ08BM8UniProtA8E5K6Reactome DB_ID: 102223251UniProt:A0A286YAE5cnot4aUniProtA0A286YAE51EQUAL575EQUALReactome DB_ID: 102223211UniProt:Q1LUD8cnot3bUniProtQ1LUD81EQUAL753EQUALReactome DB_ID: 102223171UniProt:A1A5H6cnot1UniProtA1A5H61EQUAL2376EQUALConverted from EntitySet in ReactomeReactome DB_ID: 102223611CNOT6 or CNOT6L [cytosol]Converted from EntitySet in Reactome. Each synonym is a name of a PhysicalEntity, and each XREF points to one PhysicalEntitycnot6l [cytosol]cnot6a [cytosol]UniProtA2BHJ4UniProtQ6PE30Reactome DB_ID: 102223411UniProt:A4QP78cnot11UniProtA4QP781EQUAL510EQUALConverted from EntitySet in ReactomeReactome DB_ID: 102223511Homologues of TNKS1BP1 [cytosol]Converted from EntitySet in Reactome. Each synonym is a name of a PhysicalEntity, and each XREF points to one PhysicalEntitysi:ch73-138n13.1 [cytosol]tnks1bp1 [cytosol]UniProtE9QB91UniProtF1QZU1Reactome DB_ID: 102223331UniProt:A4QN63cnot2UniProtA4QN631EQUAL540EQUALReactome DB_ID: 102223371UniProt:Q6NWL4cnot9UniProtQ6NWL41EQUAL299EQUALReactome DB_ID: 102223291UniProt:Q08CL8cnot10UniProtQ08CL81EQUAL744EQUALReactome Database ID Release 7510222373Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10222373ReactomeR-DRE-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-DRE-429896.1Reactome DB_ID: 102800191UniProt:Q9IB77btg2UniProtQ9IB771EQUAL158EQUALReactome DB_ID: 102800211BTG2:CCR4-NOT [cytosol]BTG2:CCR4-NOTReactome DB_ID: 102223731Reactome DB_ID: 1028001911EQUAL158EQUALReactome Database ID Release 7510280021Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10280021ReactomeR-DRE-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-DRE-6798046.1Reactome Database ID Release 7510280023Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10280023ReactomeR-DRE-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-DRE-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:e51331inferred by electronic annotationIEAGOIEA2.7.11PLK2 phosphorylates CENPJPLK2 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>Reactome DB_ID: 1135922Reactome DB_ID: 102170301UniProt:E7FCY1cenpjUniProtE7FCY11EQUAL1338EQUALReactome DB_ID: 102848381O-phospho-L-serine at 589 (in Homo sapiens)589EQUALO-phospho-L-serine at 595 (in Homo sapiens)595EQUAL1EQUAL1338EQUALReactome DB_ID: 293702PHYSIOL-LEFT-TO-RIGHTACTIVATIONReactome DB_ID: 10284842UniProt:E7EXD4plk2aUniProtE7EXD41EQUAL685EQUALReactome Database ID Release 7510284843Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10284843Reactome Database ID Release 7510284845Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10284845ReactomeR-DRE-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-DRE-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. 29:2395-406inferred by electronic annotationIEAGOIEA2.7.11PLK2 phosphorylates NPM1PLK2 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>Reactome DB_ID: 102848471UniProt:F1QGI4npm1aUniProtF1QGI41EQUAL294EQUALReactome DB_ID: 1135921Reactome DB_ID: 293701Reactome DB_ID: 102848501O-phospho-L-serine at 4 (in Homo sapiens)4EQUAL1EQUAL294EQUALPHYSIOL-LEFT-TO-RIGHTACTIVATIONReactome DB_ID: 102848421EQUAL685EQUALReactome Database ID Release 7510284852Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10284852ReactomeR-DRE-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-DRE-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:e9849inferred by electronic annotationIEAGOIEA2.7.11PLK3 phosphorylates CDC25CPLK3 phosphorylates CDC25CThis 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 DB_ID: 293581Converted from EntitySet in ReactomeReactome DB_ID: 101938921Homologues of CDC25C [nucleoplasm]Converted from EntitySet in Reactome. Each synonym is a name of a PhysicalEntity, and each XREF points to one PhysicalEntitycdc25b [nucleoplasm]cdc25d [nucleoplasm]UniProtB8A5N7UniProtB8A4H7Reactome DB_ID: 1135821Converted from EntitySet in ReactomeReactome DB_ID: 102849171Homologues of p-S191-CDC25C [nucleoplasm]Converted from EntitySet in Reactome. Each synonym is a name of a PhysicalEntity, and each XREF points to one PhysicalEntityphospho-cdc25d [nucleoplasm]phospho-cdc25b [nucleoplasm]PHYSIOL-LEFT-TO-RIGHTACTIVATIONReactome DB_ID: 10284921UniProt:B0S6K2plk3UniProtB0S6K21EQUAL646EQUALReactome Database ID Release 7510284922Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10284922Reactome Database ID Release 7510284924Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10284924ReactomeR-DRE-68029731Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-DRE-6802973.1PLK3 phosphorylates CDC25C at serine residue S191 within the nuclear export signal (NES). Phosphorylation of CDC25C at S191 promotes nuclear localization of CDC25C, probably by masking the NES. Nuclear accumulation of CDC25C may be important for coordination of M phase events (Bahassi et al. 2004).14968113Pubmed2004Cdc25C phosphorylation on serine 191 by Plk3 promotes its nuclear translocationBahassi, El MustaphaHennigan, Robert FMyer, David LStambrook, Peter JOncogene 23:2658-63inferred by electronic annotationIEAGOIEAReactome Database ID Release 7510305647Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10305647ReactomeR-DRE-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-DRE-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. 16:2814-2511814693Pubmed2002The 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 26:1110-21inferred by electronic annotationIEAGOIEAReactome Database ID Release 7510302869Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10302869ReactomeR-DRE-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-DRE-6791312.1GO0006977GO biological processUnder 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.inferred by electronic annotationIEAGOIEATP53 Regulates Transcription of DNA Repair GenesTP53 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>CCNK binds CDK12CCNK 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>Reactome DB_ID: 102797781UniProt:F1R6Y1cdk12UniProtF1R6Y11EQUAL1490EQUALReactome DB_ID: 101967251UniProt:F1QMB9ccnkUniProtF1QMB91EQUAL580EQUALReactome DB_ID: 102797801CCNK:CDK12 [nucleoplasm]CCNK:CDK12Reactome DB_ID: 1027977811EQUAL1490EQUALReactome DB_ID: 1019672511EQUAL580EQUALReactome Database ID Release 7510279780Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10279780ReactomeR-DRE-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-DRE-6797095.1Reactome Database ID Release 7510279782Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10279782ReactomeR-DRE-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-DRE-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. 25:2158-72inferred by electronic annotationIEAGOIEACCNK binds CDK13CCNK 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>Reactome DB_ID: 1019672511EQUAL580EQUALReactome DB_ID: 102797861UniProt:E7F092cdk13UniProtE7F0921EQUAL1512EQUALReactome DB_ID: 102797881CCNK:CDK13 [nucleoplasm]CCNK:CDK13Reactome DB_ID: 1019672511EQUAL580EQUALReactome DB_ID: 1027978611EQUAL1512EQUALReactome Database ID Release 7510279788Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10279788ReactomeR-DRE-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-DRE-6797094.1Reactome Database ID Release 7510279790Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10279790ReactomeR-DRE-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-DRE-6797100.1Cyclin K (CCNK) forms a complex with CDK13 (Blazek et al. 2011).inferred by electronic annotationIEAGOIEACCNK:CDK12 binds RNA Pol II at DNA repair genesCCNK: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>Reactome DB_ID: 102798761Elongation Complex at DNA Repair Genes [nucleoplasm]Elongation Complex at DNA Repair GenesReactome DB_ID: 101968051FACT complex [nucleoplasm]FACT complexReactome DB_ID: 101968031UniProt:A5A4L9supt16hUniProtA5A4L92EQUAL1047EQUALReactome DB_ID: 101967991UniProt:F6NLJ7ssrp1bUniProtF6NLJ72EQUAL709EQUALReactome Database ID Release 7510196805Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10196805ReactomeR-DRE-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-DRE-112417.1Reactome DB_ID: 101967851UniProt:A0A2R8RXT0ellUniProtA0A2R8RXT01EQUAL621EQUALReactome DB_ID: 101929841TFIIH [nucleoplasm]TFIIHReactome DB_ID: 101929701UniProt:Q7ZVV4gtf2h2UniProtQ7ZVV41EQUAL395EQUALReactome DB_ID: 101929781UniProt:Q66I03gtf2h1UniProtQ66I031EQUAL548EQUALConverted from EntitySet in ReactomeReactome DB_ID: 101929661Homologues of GTF2H3 [nucleoplasm]Converted from EntitySet in Reactome. Each synonym is a name of a PhysicalEntity, and each XREF points to one PhysicalEntityGTF2H3 [nucleoplasm]gtf2h3 [nucleoplasm]UniProtA0A2R8QHR5UniProtA5WWE3Reactome DB_ID: 101929561UniProt:Q7ZVV1ercc3UniProtQ7ZVV11EQUAL782EQUALReactome DB_ID: 101929481CAK [nucleoplasm]CAKReactome DB_ID: 101929421UniProt:A2BGI0ccnhUniProtA2BGI01EQUAL323EQUALReactome DB_ID: 101929381UniProt:Q2V6H0cdk7UniProtQ2V6H01EQUAL346EQUALReactome DB_ID: 101929461UniProt:B8A5G8mnat1UniProtB8A5G81EQUAL309EQUALReactome Database ID Release 7510192948Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10192948ReactomeR-DRE-692211Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-DRE-69221.1Reactome DB_ID: 101929521UniProt:F1Q5E7ercc2UniProtF1Q5E71EQUAL760EQUALReactome DB_ID: 101929741UniProt:A0A286YAJ0gtf2h4UniProtA0A286YAJ01EQUAL462EQUALReactome DB_ID: 101929821UniProt:Q5SNQ6gtf2h5UniProtQ5SNQ61EQUAL71EQUALReactome Database ID Release 7510192984Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10192984ReactomeR-DRE-1096341Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-DRE-109634.1Reactome DB_ID: 102798741Hyperphosphorylated RNA Pol II at DNA repair genes [nucleoplasm]Hyperphosphorylated RNA Pol II at DNA repair genesReactome DB_ID: 101967551NELF complex [nucleoplasm]NELF complexReactome DB_ID: 101967411UniProt:A0A0R4IBP1nelfaUniProtA0A0R4IBP11EQUAL528EQUALReactome DB_ID: 101967531UniProt:A0A2R8QPV7nelfeUniProtA0A2R8QPV71EQUAL380EQUALReactome DB_ID: 101967491UniProt:F1Q889nelfcdUniProtF1Q8891EQUAL590EQUALReactome DB_ID: 101967451UniProt:A0A0R4IWG6nelfbUniProtA0A0R4IWG61EQUAL580EQUALReactome Database ID Release 7510196755Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10196755ReactomeR-DRE-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-DRE-112432.1Reactome DB_ID: 101967651UniProt:E7FFL3ctdp1UniProtE7FFL31EQUAL961EQUALReactome DB_ID: 102798721Ghost homologue of Nascent mRNAs of DNA repair genes regulated by CDK12 [nucleoplasm]Ghost homologue of Nascent mRNAs of DNA repair genes regulated by CDK12Reactome DB_ID: 101967171RNA Polymerase II holoenzyme complex (hyperphosphorylated):TFIIF complex [nucleoplasm]RNA Polymerase II holoenzyme complex (hyperphosphorylated):TFIIF complexReactome DB_ID: 101967151RNA Polymerase II holoenzyme complex (hyperphosphorylated) [nucleoplasm]RNA Polymerase II holoenzyme complex (hyperphosphorylated)Reactome DB_ID: 101910761UniProt:Q1LVK2polr2iUniProtQ1LVK21EQUAL125EQUALReactome DB_ID: 101911001UniProt:F1RDV9polr2kUniProtF1RDV91EQUAL58EQUALReactome DB_ID: 101910801UniProt:A0A0R4IXL0polr2bUniProtA0A0R4IXL01EQUAL1174EQUALReactome DB_ID: 101910881UniProt:Q7ZW41polr2gUniProtQ7ZW411EQUAL172EQUALReactome DB_ID: 101911121UniProt:A5D6S6polr2lUniProtA5D6S61EQUAL67EQUALReactome DB_ID: 101910961UniProt:Q568H8polr2hUniProtQ568H82EQUAL150EQUALReactome DB_ID: 101910921UniProt:Q7ZV11polr2cUniProtQ7ZV112EQUAL275EQUALReactome DB_ID: 101911081UniProt:A0A2R8PUZ9polr2fUniProtA0A2R8PUZ92EQUAL127EQUALReactome DB_ID: 101910841UniProt:Q6DRG4polr2dUniProtQ6DRG41EQUAL142EQUALReactome DB_ID: 101910721UniProt:Q4VBU5polr2jUniProtQ4VBU51EQUAL117EQUALReactome DB_ID: 101911041UniProt:Q6DEG5polr2ebUniProtQ6DEG51EQUAL210EQUALReactome DB_ID: 101967131UniProt:A0A0R4IMS9polr2aUniProtA0A0R4IMS9O-phospho-L-serine at 5 (in Homo sapiens)5EQUALO-phospho-L-serine at 2 (in Homo sapiens)2EQUAL1EQUAL1970EQUALReactome Database ID Release 7510196715Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10196715ReactomeR-DRE-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-DRE-109909.1Reactome DB_ID: 101911241TFIIF [nucleoplasm]TFIIFReactome DB_ID: 101911181UniProt:Q5PNQ6gtf2f1UniProtQ5PNQ62EQUAL517EQUALReactome DB_ID: 101911221UniProt:B8JHR3gtf2f2aUniProtB8JHR32EQUAL249EQUALReactome Database ID Release 7510191124Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10191124ReactomeR-DRE-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-DRE-109631.1Reactome Database ID Release 7510196717Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10196717ReactomeR-DRE-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-DRE-113425.1Reactome DB_ID: 101967371P-TEFb complex [nucleoplasm]P-TEFb complexReactome DB_ID: 101967211UniProt:Q7T3L5UniProtQ7T3L51EQUAL372EQUALConverted from EntitySet in ReactomeReactome DB_ID: 101967351CCNT1,CCNT2,CCNK [nucleoplasm]Converted from EntitySet in Reactome. Each synonym is a name of a PhysicalEntity, and each XREF points to one PhysicalEntityccnk [nucleoplasm]ccnt1 [nucleoplasm]ccnt2a [nucleoplasm]UniProtB8A521UniProtA0A2R8QAB1Reactome Database ID Release 7510196737Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10196737ReactomeR-DRE-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-DRE-112431.1Reactome DB_ID: 101967611DSIF complex [nucleoplasm]DSIF complexReactome DB_ID: 101948821UniProt:Q9DDT5supt5hUniProtQ9DDT5phosphorylated residue at unknown positionphosphorylated residue [MOD:00696]1EQUAL1087EQUALReactome DB_ID: 101967591UniProt:Q6DGQ0supt4h1UniProtQ6DGQ01EQUAL117EQUALReactome Database ID Release 7510196761Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10196761ReactomeR-DRE-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-DRE-112420.1Reactome DB_ID: 102798701Ghost homologue of DNA repair genes regulated by CDK12 [nucleoplasm]Ghost homologue of DNA repair genes regulated by CDK12Reactome Database ID Release 7510279874Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10279874ReactomeR-DRE-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-DRE-6797609.1Reactome DB_ID: 101968381Elongin Complex [nucleoplasm]Elongin ComplexReactome DB_ID: 101968341Elongin B:C complex [nucleoplasm]Elongin B:C complexReactome DB_ID: 101968321Ghost homologue of TCEB2 [nucleoplasm]Ghost homologue of TCEB2Converted from EntitySet in ReactomeReactome DB_ID: 101968301Homologues of TCEB1 [nucleoplasm]Converted from EntitySet in Reactome. Each synonym is a name of a PhysicalEntity, and each XREF points to one PhysicalEntityTCEB1 [nucleoplasm]elocb [nucleoplasm]eloca [nucleoplasm]UniProtA0A2R8QG16UniProtA0A286YBA4UniProtQ66IB1Reactome Database ID Release 7510196834Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10196834ReactomeR-DRE-1124241Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-DRE-112424.1Reactome DB_ID: 101968361Ghost homologue of Elongin A [nucleoplasm]Ghost homologue of Elongin AReactome Database ID Release 7510196838Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10196838ReactomeR-DRE-1124251Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-DRE-112425.1Reactome DB_ID: 101967951UniProt:A0A2R8Q7Y8tcea1UniProtA0A2R8Q7Y81EQUAL301EQUALReactome Database ID Release 7510279876Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10279876ReactomeR-DRE-67976111Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-DRE-6797611.1Reactome DB_ID: 102797801Reactome DB_ID: 102798781CCNK:CDK12:Elongation Complex at DNA Repair Genes [nucleoplasm]CCNK:CDK12:Elongation Complex at DNA Repair GenesReactome DB_ID: 102798761Reactome DB_ID: 102797801Reactome Database ID Release 7510279878Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10279878ReactomeR-DRE-67976141Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-DRE-6797614.1Reactome Database ID Release 7510279896Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10279896ReactomeR-DRE-67976161Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-DRE-6797616.1The complex of CDK12 and CCNK (cyclin K) associates with the RNA polymerase II (RNA Pol II) elongation complex at DNA repair genes encoding long primary transcripts, such as BRCA1, ATR, FANCI, FANCD2, ATM, MDC1, CHEK1, RAD51D and APEX1 (Blazek et al. 2011, Bartkowiak and Greenleaf 2015, Ekumi et al. 2015, Liang et al. 2015).25561469Pubmed2015Characterization of human cyclin-dependent kinase 12 (CDK12) and CDK13 complexes in C-terminal domain phosphorylation, gene transcription, and RNA processingLiang, KaiweiGao, XinGilmore, Joshua MFlorens, Laurence AWashburn, Michael PSmith, EdwinShilatifard, AMol. Cell. Biol. 35:928-3825712099Pubmed2015Ovarian carcinoma CDK12 mutations misregulate expression of DNA repair genes via deficient formation and function of the Cdk12/CycK complexEkumi, Kingsley MPaculova, HanaLenasi, TinaPospichalova, VendulaBösken, Christian ARybarikova, JanaBryja, VGeyer, MatthiasBlazek, DaliborBarboric, MatjazNucleic Acids Res. 43:2575-8925429106Pubmed2015Expression, purification, and identification of associated proteins of the full-length hCDK12/CyclinK complexBartkowiak, BartlomiejGreenleaf, Arno LJ. Biol. Chem. 290:1786-95inferred by electronic annotationIEAGOIEA2.7.11.22CDK12 phosphorylates RNA Pol II CTD at DNA repair genesCDK12 phosphorylates RNA Pol II CTD 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&