BioPAX pathway converted from "p53-Dependent G1/S DNA damage checkpoint" in the Reactome database. p53-Dependent G1/S DNA damage checkpoint p53-Dependent G1/S DNA damage checkpoint 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> p53-Dependent G1 DNA Damage Response p53-Dependent G1 DNA Damage Response 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> Stabilization of p53 Stabilization of p53 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> 2.7.11.1 ATM phosphorylates TP53 at S15 ATM phosphorylates TP53 at S15 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: 10307943 1 nucleoplasm GO 0005654 TP53 Tetramer [nucleoplasm] TP53 Tetramer Reactome DB_ID: 10307573 4 UniProt:Q9TUB2 Reactome http://www.reactome.org Sus scrofa NCBI Taxonomy 9823 UniProt Q9TUB2 Chain Coordinates 1 EQUAL 393 EQUAL Reactome Database ID Release 82 10307943 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10307943 Reactome R-SSC-3209194 1 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-SSC-3209194.1 Reactome DB_ID: 29358 4 ATP(4-) [ChEBI:30616] ATP(4-) Adenosine 5'-triphosphate atp ATP ChEBI 30616 Reactome DB_ID: 10250095 1 p-S15-TP53 Tetramer [nucleoplasm] p-S15-TP53 Tetramer Reactome DB_ID: 10250093 4 O-phospho-L-serine at 15 (in Homo sapiens) 15 EQUAL O-phospho-L-serine [MOD:00046] 1 EQUAL 393 EQUAL Reactome Database ID Release 82 10250095 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10250095 Reactome R-SSC-349474 1 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-SSC-349474.1 Reactome DB_ID: 113582 4 ADP(3-) [ChEBI:456216] ADP(3-) ADP trianion 5&apos;-O-[(phosphonatooxy)phosphinato]adenosine ADP ChEBI 456216 PHYSIOL-LEFT-TO-RIGHT ACTIVATION Reactome DB_ID: 10250145 UniProt:F1SV20 ATM UniProt F1SV20 O-phospho-L-serine at 1981 (in Homo sapiens) 1981 EQUAL N6-acetyl-L-lysine at 3016 (in Homo sapiens) 3016 EQUAL N6-acetyl-L-lysine [MOD:00064] 1 EQUAL 3056 EQUAL GO 0004674 GO molecular function Reactome Database ID Release 82 10271428 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10271428 Reactome Database ID Release 82 10322896 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10322896 Reactome R-SSC-5693609 1 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-SSC-5693609.1 In response to DNA double strand breaks, serine at position 15 of the TP53 (p53) tumor suppressor protein is rapidly phosphorylated by the ATM kinase. This serves to stabilize the p53 protein. A rise in the levels of the p53 protein induces the expression of p21 cyclin-dependent kinase inhibitor. This prevents the normal progression from G1 to S phase, thus providing a check on replication of damaged DNA (Banin et al. 1998, Canman et al. 1998, Khanna et al. 1998). 9733515 Pubmed 1998 Activation of the ATM kinase by ionizing radiation and phosphorylation of p53. Canman, CE Lim, DS Taya, Y Tamai, K Sakaguchi, K Appella, E Kastan, MB Siliciano, JD Science 281:1677-9 9733514 Pubmed 1998 Enhanced phosphorylation of p53 by ATM in response to DNA damage. Banin, S Moyal, L Shieh, S Taya, Y Anderson, CW Chessa, L Smorodinsky, NI Prives, C Reiss, Y Shiloh, Y Ziv, Y Science 281:1674-7 9843217 Pubmed 1998 ATM associates with and phosphorylates p53: mapping the region of interaction. Khanna, Kum Kum Keating, KE Kozlov, S Scott, S Gatei, M Hobson, K Taya, Y Gabrielli, B Chan, D Lees-Miller, SP Lavin, MF Nat Genet 20:398-400 inferred by electronic annotation IEA GO IEA 2.7.11.1 CHEK2 phosphorylates TP53 CHEK2 phosphorylates TP53 Phosphorylation of p53 by ATM-activated Chk2 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: 10250095 1 Reactome DB_ID: 29358 4 Reactome DB_ID: 10250100 1 p-S15,S20-TP53 Tetramer [nucleoplasm] p-S15,S20-TP53 Tetramer Reactome DB_ID: 10250098 4 O-phospho-L-serine at 20 (in Homo sapiens) 20 EQUAL O-phospho-L-serine at 15 (in Homo sapiens) 15 EQUAL 1 EQUAL 393 EQUAL Reactome Database ID Release 82 10250100 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10250100 Reactome R-SSC-3222171 1 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-SSC-3222171.1 Reactome DB_ID: 113582 4 PHYSIOL-LEFT-TO-RIGHT ACTIVATION Reactome DB_ID: 10250085 UniProt:A0A287A7U1 CHEK2 UniProt A0A287A7U1 O-phospho-L-threonine at 68 (in Homo sapiens) 68 EQUAL O-phospho-L-threonine [MOD:00047] O-phospho-L-serine at 379 (in Homo sapiens) 379 EQUAL O-phospho-L-threonine at 383 (in Homo sapiens) 383 EQUAL O-phospho-L-threonine at 387 (in Homo sapiens) 387 EQUAL 1 EQUAL 543 EQUAL Reactome Database ID Release 82 10250086 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10250086 Reactome Database ID Release 82 10250102 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10250102 Reactome R-SSC-69685 1 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-SSC-69685.1 CHEK2 (Chk2) phosphorylates TP53 (p53) at serine residue S20 (Hirao et al. 2000, Shieh et al. 2000, Chehab et al. 2000). Phosphorylation of TP53 at serine residue S20 is necessary for DNA damage-induced TP53 stabilization as it compromises the interaction of TP53 with the ubiquitin ligase MDM2 (Chehab et al. 1999, Chehab et al. 2000). S20 phosphorylation is also required for the induction of TP53-dependent transcripts in response to DNA damage (Hirao et al. 2000). 10673500 Pubmed 2000 Chk2/hCds1 functions as a DNA damage checkpoint in G(1) by stabilizing p53. Chehab, NH Malikzay, A Appel, M Halazonetis, TD Genes Dev 14:278-88 10710310 Pubmed 2000 DNA damage-induced activation of p53 by the checkpoint kinase Chk2. Hirao, A Kong, YY Matsuoka, S Wakeham, A Ruland, J Yoshida, H Liu, D Elledge, SJ Mak, TW Science 287:1824-7 10673501 Pubmed 2000 The human homologs of checkpoint kinases Chk1 and Cds1 (Chk2) phosphorylate p53 at multiple DNA damage-inducible sites. Shieh, SY Ahn, J Tamai, K Taya, Y Prives, C Genes Dev 14:289-300 10570149 Pubmed 1999 Phosphorylation of Ser-20 mediates stabilization of human p53 in response to DNA damage Chehab, N H Malikzay, A Stavridi, E S Halazonetis, T D Proc. Natl. Acad. Sci. U.S.A. 96:13777-82 inferred by electronic annotation IEA GO IEA 2.7.11.1 ATM phosphorylates MDM2 ATM phosphorylates MDM2 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: 29358 4 Reactome DB_ID: 10307931 1 UniProt:A0A287BEY7 MDM2 UniProt A0A287BEY7 O-phospho-L-serine at 166 (in Homo sapiens) 166 EQUAL O-phospho-L-serine at 188 (in Homo sapiens) 188 EQUAL 1 EQUAL 491 EQUAL Reactome DB_ID: 113582 4 Reactome DB_ID: 10330033 1 O-phospho-L-serine at 166 (in Homo sapiens) 166 EQUAL O-phospho-L-serine at 188 (in Homo sapiens) 188 EQUAL O-phospho-L-serine at 386 (in Homo sapiens) 386 EQUAL O-phospho-L-serine at 395 (in Homo sapiens) 395 EQUAL O-phospho-L-serine at 407 (in Homo sapiens) 407 EQUAL O-phospho-L-threonine at 419 (in Homo sapiens) 419 EQUAL 1 EQUAL 491 EQUAL PHYSIOL-LEFT-TO-RIGHT ACTIVATION Reactome DB_ID: 10250145 O-phospho-L-serine at 1981 (in Homo sapiens) 1981 EQUAL N6-acetyl-L-lysine at 3016 (in Homo sapiens) 3016 EQUAL 1 EQUAL 3056 EQUAL Reactome Database ID Release 82 10330035 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10330035 Reactome R-SSC-6804955 1 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-SSC-6804955.1 ATM phosphorylates MDM2 on three serine residues (S386, S395, S407) and one threonine residue (T419) in vicinity to the RING domain. ATM-mediated phosphorylation of MDM2 in response to DNA damage (DNA double strand breaks) prevents MDM2 dimerization, binding of TP53 (p53) and MDM2-mediated ubiquitination of TP53 (Cheng et al. 2009, Cheng et al. 2011). 21986495 Pubmed 2011 Regulation of MDM2 E3 ligase activity by phosphorylation after DNA damage Cheng, Qian Cross, Brittany Li, Baozong Chen, Lihong Li, Zhenyu Chen, Jiandong Mol. Cell. Biol. 31:4951-63 19816404 Pubmed 2009 ATM activates p53 by regulating MDM2 oligomerization and E3 processivity Cheng, Qian Chen, Lihong Li, Zhenyu Lane, William S Chen, Jiandong EMBO J. 28:3857-67 inferred by electronic annotation IEA GO IEA MDM2 forms homo- or heterodimers MDM2 forms homo- or heterodimers 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: 10307931 3 O-phospho-L-serine at 166 (in Homo sapiens) 166 EQUAL O-phospho-L-serine at 188 (in Homo sapiens) 188 EQUAL 1 EQUAL 491 EQUAL Reactome DB_ID: 10307933 1 p-S166,S188-MDM2 dimer [nucleoplasm] p-S166,S188-MDM2 dimer Reactome DB_ID: 10307931 2 O-phospho-L-serine at 166 (in Homo sapiens) 166 EQUAL O-phospho-L-serine at 188 (in Homo sapiens) 188 EQUAL 1 EQUAL 491 EQUAL Reactome Database ID Release 82 10307933 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10307933 Reactome R-SSC-6804933 1 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-SSC-6804933.1 Reactome Database ID Release 82 10330022 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10330022 Reactome R-SSC-6804741 1 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-SSC-6804741.1 To efficiently function as an E3 ubiquitin ligase, MDM2 has to form dimers or higher order oligomers. MDM2 can homodimerize (Cheng et al. 2011) or heterodimerize with MDM4 (MDMX) (Sharp et al. 1999, Huang et al. 2011, Pant et al. 2011). Dimerization involves the RING domain of MDM2 and/or MDM4. Heterodimers of MDM2 and MDM4 may be particularly important during embryonic development (Pant et al. 2011). 21730132 Pubmed 2011 Heterodimerization of Mdm2 and Mdm4 is critical for regulating p53 activity during embryogenesis but dispensable for p53 and Mdm2 stability Pant, Vinod Xiong, Shunbin Iwakuma, Tomoo Quintás-Cardama, Alfonso Lozano, Guillermina Proc. Natl. Acad. Sci. U.S.A. 108:11995-2000 10608892 Pubmed 1999 Stabilization of the MDM2 oncoprotein by interaction with the structurally related MDMX protein Sharp, D A Kratowicz, S A Sank, M J George, D L J. Biol. Chem. 274:38189-96 21730163 Pubmed 2011 The p53 inhibitors MDM2/MDMX complex is required for control of p53 activity in vivo Huang, Lei Yan, Zheng Liao, Xiaodong Li, Yuan Yang, Jie Wang, Zhu-Gang Zuo, Yong Kawai, Hidehiko Shadfan, Miriam Ganapathy, Suthakar Yuan, Zhi-Min Proc. Natl. Acad. Sci. U.S.A. 108:12001-6 inferred by electronic annotation IEA GO IEA INHIBITION Reactome Database ID Release 82 10330023 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10330023 Reactome DB_ID: 10250145 O-phospho-L-serine at 1981 (in Homo sapiens) 1981 EQUAL N6-acetyl-L-lysine at 3016 (in Homo sapiens) 3016 EQUAL 1 EQUAL 3056 EQUAL Ubiquitinated TP53 translocates to the cytosol Ubiquitinated TP53 translocates to the cytosol 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: 10307941 1 PolyUb-TP53 Tetramer [nucleoplasm] PolyUb-TP53 Tetramer Reactome DB_ID: 10307939 4 ubiquitinylated lysine (PolyUb [nucleoplasm]) at unknown position ubiquitinylated lysine [MOD:01148] 1 EQUAL 393 EQUAL Reactome Database ID Release 82 10307941 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10307941 Reactome R-SSC-3209186 1 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-SSC-3209186.1 Reactome DB_ID: 10326286 1 cytosol GO 0005829 PolyUb-TP53 Tetramer [cytosol] PolyUb-TP53 Tetramer Reactome DB_ID: 10326284 4 ubiquitinylated lysine (PolyUb [nucleoplasm]) at unknown position 1 EQUAL 393 EQUAL Reactome Database ID Release 82 10326286 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10326286 Reactome R-SSC-8856287 1 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-SSC-8856287.1 Reactome Database ID Release 82 10326288 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10326288 Reactome R-SSC-6793685 1 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-SSC-6793685.1 Upon MDM2-mediated ubiquitination, TP53 is exported from the nucleus to the cytosol. TP53 nuclear export requires the nuclear export sequence (NES) of TP53, but not the NES of MDM2 (Boyd et al. 2000. Geyer et al. 2000). 10980696 Pubmed 2000 The MDM2 RING-finger domain is required to promote p53 nuclear export Geyer, R K Yu, Z K Maki, C G Nat. Cell Biol. 2:569-73 10980695 Pubmed 2000 An intact HDM2 RING-finger domain is required for nuclear exclusion of p53 Boyd, S D Tsai, K Y Jacks, T Nat. Cell Biol. 2:563-8 inferred by electronic annotation IEA GO IEA Autodegradation of the E3 ubiquitin ligase COP1 Autodegradation of the E3 ubiquitin ligase COP1 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> 2.7.11.1 Phosphorylation of COP1 at Ser-387 by ATM Phosphorylation of COP1 at Ser-387 by ATM 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: 29358 1 Reactome DB_ID: 10271427 1 UniProt:F1S705 COP1 UniProt F1S705 1 EQUAL 731 EQUAL Reactome DB_ID: 113582 1 Reactome DB_ID: 10270947 1 O-phospho-L-serine at 387 (in Homo sapiens) 387 EQUAL 1 EQUAL 731 EQUAL PHYSIOL-LEFT-TO-RIGHT ACTIVATION Reactome DB_ID: 10250145 O-phospho-L-serine at 1981 (in Homo sapiens) 1981 EQUAL N6-acetyl-L-lysine at 3016 (in Homo sapiens) 3016 EQUAL 1 EQUAL 3056 EQUAL Reactome Database ID Release 82 10271430 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10271430 Reactome R-SSC-349444 1 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-SSC-349444.1 ATM phosphorylates COP1 on Ser387 in response to DNA damage (Dornan et al., 2006). 16931761 Pubmed 2006 ATM engages autodegradation of the E3 ubiquitin ligase COP1 after DNA damage Dornan, D Shimizu, H Mah, A Dudhela, T Eby, M O'Rourke, K Seshagiri, S Dixit, VM Science 313:1122-6 inferred by electronic annotation IEA GO IEA Dissociation of the COP1-p53 complex Dissociation of the COP1-p53 complex 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: 10270953 1 p-S387-RFWD2:p-S15-TP53 [nucleoplasm] p-S387-RFWD2:p-S15-TP53 Reactome DB_ID: 10250095 1 Reactome DB_ID: 10270947 1 O-phospho-L-serine at 387 (in Homo sapiens) 387 EQUAL 1 EQUAL 731 EQUAL Reactome Database ID Release 82 10270953 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10270953 Reactome R-SSC-349420 1 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-SSC-349420.1 Reactome DB_ID: 10250095 1 Reactome DB_ID: 10270947 1 O-phospho-L-serine at 387 (in Homo sapiens) 387 EQUAL 1 EQUAL 731 EQUAL Reactome Database ID Release 82 10270955 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10270955 Reactome R-SSC-264435 1 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-SSC-264435.1 ATM-dependent phosphorylation of COP1 on Ser(387) results in disruption of the COP1-p53 complex (Dornan et al., 2006) inferred by electronic annotation IEA GO IEA Translocation of COP1 from the nucleus to the cytoplasm Translocation of COP1 from the nucleus to the cytoplasm 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: 10270947 1 O-phospho-L-serine at 387 (in Homo sapiens) 387 EQUAL 1 EQUAL 731 EQUAL Reactome DB_ID: 10270949 1 O-phospho-L-serine at 387 (in Homo sapiens) 387 EQUAL 1 EQUAL 731 EQUAL Reactome Database ID Release 82 10270951 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10270951 Reactome R-SSC-264418 1 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-SSC-264418.1 Ionizing radiation results in an ATM-dependent movement of COP1 from the nucleus to the cytoplasm (Dornan et al., 2006). inferred by electronic annotation IEA GO IEA 6.3.2.19 Autoubiquitination of phospho-COP1(Ser-387 ) Autoubiquitination of phospho-COP1(Ser-387 ) 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> Converted from EntitySet in Reactome Reactome DB_ID: 10249581 4 Ub [cytosol] Converted from EntitySet in Reactome. Each synonym is a name of a PhysicalEntity, and each XREF points to one PhysicalEntity RPS27A [cytosol] UBC [cytosol] UBA52 [cytosol] UniProt A0A287AZA7 UniProt P0CG68 UniProt P63053 Reactome DB_ID: 10270949 1 O-phospho-L-serine at 387 (in Homo sapiens) 387 EQUAL 1 EQUAL 731 EQUAL Reactome DB_ID: 10270957 1 ubiquitinated phospho-COP1(ser-387) [cytosol] ubiquitinated phospho-COP1(ser-387) Converted from EntitySet in Reactome Reactome DB_ID: 10249581 4 Reactome DB_ID: 10270949 1 O-phospho-L-serine at 387 (in Homo sapiens) 387 EQUAL 1 EQUAL 731 EQUAL Reactome Database ID Release 82 10270957 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10270957 Reactome R-SSC-349433 1 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-SSC-349433.1 PHYSIOL-LEFT-TO-RIGHT ACTIVATION Reactome DB_ID: 10270949 O-phospho-L-serine at 387 (in Homo sapiens) 387 EQUAL 1 EQUAL 731 EQUAL GO 0004842 GO molecular function Reactome Database ID Release 82 10270958 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10270958 Reactome Database ID Release 82 10270960 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10270960 Reactome R-SSC-264444 1 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-SSC-264444.1 ATM phosphorylation promotes autoubiquitination of COP1 in vitro (Dornan et al., 2006). The number of ubiquitin molecules shown in this reaction is set arbitrarily at 4. inferred by electronic annotation IEA GO IEA Proteasome mediated degradation of COP1 Proteasome mediated degradation of COP1 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: 10270957 1 Converted from EntitySet in Reactome Reactome DB_ID: 10249581 4 PHYSIOL-LEFT-TO-RIGHT ACTIVATION Reactome DB_ID: 10249683 26S proteasome [cytosol] 26S proteasome Reactome DB_ID: 10249613 1 UniProt:A1XQU1 PSMB7 UniProt A1XQU1 44 EQUAL 277 EQUAL Reactome DB_ID: 10249619 1 UniProt:F2Z5J1 PSMC1 UniProt F2Z5J1 2 EQUAL 440 EQUAL Reactome DB_ID: 10249639 1 UniProt:F1RKW8 PSMD11 UniProt F1RKW8 2 EQUAL 422 EQUAL Reactome DB_ID: 10249663 1 UniProt:F1SGM3 PSME2 UniProt F1SGM3 2 EQUAL 239 EQUAL Reactome DB_ID: 10249603 1 UniProt:A0A5G2R6J1 PSMB2 UniProt A0A5G2R6J1 1 EQUAL 201 EQUAL Reactome DB_ID: 10249591 1 UniProt:A0A5G2QL81 PSMA4 UniProt A0A5G2QL81 1 EQUAL 261 EQUAL Reactome DB_ID: 10249601 1 UniProt:A0A287BRV0 PSMB10 UniProt A0A287BRV0 40 EQUAL 273 EQUAL Reactome DB_ID: 10249633 1 UniProt:A0A287BG14 PSMC6 UniProt A0A287BG14 1 EQUAL 389 EQUAL Reactome DB_ID: 10249661 1 UniProt:Q64L94 PSME1 UniProt Q64L94 1 EQUAL 249 EQUAL Reactome DB_ID: 10249615 1 Ghost homologue of PSMB8 [cytosol] Ghost homologue of PSMB8 Reactome DB_ID: 10249679 1 UniProt:F1S9C7 PSMB11 UniProt F1S9C7 50 EQUAL 300 EQUAL Converted from EntitySet in Reactome Reactome DB_ID: 10249631 1 Homologues of PSMC5 [cytosol] Converted from EntitySet in Reactome. Each synonym is a name of a PhysicalEntity, and each XREF points to one PhysicalEntity PSMC5 [cytosol] PSMC5 [cytosol] UniProt P62197 UniProt A0A5G2QJH1 Reactome DB_ID: 10249587 1 UniProt:A0A5G2QZH5 PSMA2 UniProt A0A5G2QZH5 2 EQUAL 234 EQUAL Reactome DB_ID: 10249599 1 UniProt:A0A287BPP9 PSMB1 UniProt A0A287BPP9 29 EQUAL 241 EQUAL Reactome DB_ID: 10249649 1 UniProt:A0A288CG47 PSMD4 UniProt A0A288CG47 1 EQUAL 377 EQUAL Reactome DB_ID: 10249605 1 UniProt:A0A286ZN52 PSMB3 UniProt A0A286ZN52 2 EQUAL 205 EQUAL Reactome DB_ID: 10249611 1 UniProt:A0A5G2R4Y9 PSMB6 UniProt A0A5G2R4Y9 35 EQUAL 239 EQUAL Reactome DB_ID: 10249645 1 Ghost homologue of PSMD2 [cytosol] Ghost homologue of PSMD2 Reactome DB_ID: 10249675 1 UniProt:F1SBA5 PSMA8 UniProt F1SBA5 1 EQUAL 256 EQUAL Reactome DB_ID: 10249671 1 UniProt:A0A287APQ3 PSME4 UniProt A0A287APQ3 1 EQUAL 1843 EQUAL Reactome DB_ID: 10249641 1 UniProt:A0A480SMR6 PSMD12 UniProt A0A480SMR6 2 EQUAL 456 EQUAL Reactome DB_ID: 10249585 1 UniProt:A0A5G2QI19 PSMA1 UniProt A0A5G2QI19 1 EQUAL 263 EQUAL Reactome DB_ID: 10249597 1 UniProt:A0A287BRR7 PSMA7 UniProt A0A287BRR7 1 EQUAL 248 EQUAL Reactome DB_ID: 10249617 1 UniProt:Q2PYM7 PSMB9 UniProt Q2PYM7 21 EQUAL 219 EQUAL Reactome DB_ID: 10249621 1 UniProt:F1SB53 PSMC2 UniProt F1SB53 2 EQUAL 433 EQUAL Reactome DB_ID: 10249659 1 UniProt:A0A286ZLP7 PSMD9 UniProt A0A286ZLP7 1 EQUAL 223 EQUAL Reactome DB_ID: 10249653 1 UniProt:F1SGF1 PSMD6 UniProt F1SGF1 1 EQUAL 389 EQUAL Reactome DB_ID: 10249595 1 Ghost homologue of PSMA6 [cytosol] Ghost homologue of PSMA6 Reactome DB_ID: 10249665 1 UniProt:P61291 PSME3 UniProt P61291 2 EQUAL 254 EQUAL Reactome DB_ID: 10249607 1 Ghost homologue of PSMB4 [cytosol] Ghost homologue of PSMB4 Reactome DB_ID: 10249609 1 UniProt:A0A286ZS34 UniProt A0A286ZS34 60 EQUAL 263 EQUAL Reactome DB_ID: 10249657 1 UniProt:A0A287B5Q7 PSMD8 UniProt A0A287B5Q7 1 EQUAL 350 EQUAL Reactome DB_ID: 10249593 1 UniProt:F2Z5K2 PSMA5 UniProt F2Z5K2 1 EQUAL 241 EQUAL Reactome DB_ID: 10249667 1 UniProt:F1S870 PSMF1 UniProt F1S870 1 EQUAL 271 EQUAL Reactome DB_ID: 10249623 1 UniProt:A0A5G2QSU8 PSMC3 UniProt A0A5G2QSU8 1 EQUAL 439 EQUAL Reactome DB_ID: 10249681 1 Ghost homologue of SEM1 [cytosol] Ghost homologue of SEM1 Reactome DB_ID: 10249589 1 UniProt:A0A5G2QWE9 PSMA3 UniProt A0A5G2QWE9 2 EQUAL 255 EQUAL Reactome DB_ID: 10249637 1 UniProt:A0A287BTN9 PSMD10 UniProt A0A287BTN9 1 EQUAL 226 EQUAL Reactome DB_ID: 10249651 1 UniProt:A0A480QIP5 PSMD5 UniProt A0A480QIP5 2 EQUAL 504 EQUAL Reactome DB_ID: 10249625 1 UniProt:A0A287B4P8 PSMC4 UniProt A0A287B4P8 1 EQUAL 418 EQUAL Reactome DB_ID: 10249643 1 UniProt:A0A5G2R6X9 PSMD13 UniProt A0A5G2R6X9 1 EQUAL 376 EQUAL Reactome DB_ID: 10249583 1 UniProt:A0A480DPN6 PSMD14 UniProt A0A480DPN6 1 EQUAL 310 EQUAL Reactome DB_ID: 10249647 1 UniProt:F1RXA7 PSMD3 UniProt F1RXA7 1 EQUAL 534 EQUAL Reactome DB_ID: 10249655 1 UniProt:A0A287AEH0 PSMD7 UniProt A0A287AEH0 1 EQUAL 324 EQUAL Reactome DB_ID: 10249635 1 UniProt:F1SMW9 PSMD1 UniProt F1SMW9 1 EQUAL 953 EQUAL Reactome Database ID Release 82 10249683 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10249683 Reactome R-SSC-68819 1 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-SSC-68819.1 GO 0004175 GO molecular function Reactome Database ID Release 82 10249684 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10249684 Reactome Database ID Release 82 10270962 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10270962 Reactome R-SSC-264458 1 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-SSC-264458.1 Autoubiquitinated COP1 is degraded by the proteasome. The number of ubiquitin molecules shown in this reaction is arbitrarily set at 4. (Dornan et al., 2006). inferred by electronic annotation IEA GO IEA Reactome Database ID Release 82 10350816 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10350816 Reactome R-SSC-349425 1 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-SSC-349425.1 COP1 is one of several E3 ubiquitin ligases responsible for the tight regulation of p53 abundance. Following DNA damage, COP1 dissociates from p53 and is inactivated by autodegradation via a pathway involving ATM phosphorylation of COP1 on Ser(387), autoubiquitination and proteasome mediated degradation. Destruction of COP1 results in abrogation of the ubiquitination and degradation of p53 (Dornan et al., 2006). inferred by electronic annotation IEA GO IEA Reactome Database ID Release 82 10349448 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10349448 Reactome R-SSC-69541 1 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-SSC-69541.1 Later studies pin-pointed that a single serine (Ser-15) was phosphorylated by ATM and phosphorylation of Ser-15 was rapidly-induced in IR-treated cells and this response was ATM-dependent (Canman et al, 1998; Banin et al, 1998 and Khanna et al, 1998). ATM also regulates the phosphorylation of p53 at other sites, especially Ser-20, by activating other serine/threonine kinases in response to IR (Chehab et al, 2000; Shieh et al, 2000; Hirao et al 2000). Phosphorylation of p53 at Ser-20 interferes with p53-MDM2 interaction. MDM2 is transcriptionally activated by p53 and is a negative regulator of p53 that targets it for degradation (Haupt et al, 1997; Kubbutat et al, 1997). In addition modification of MDM2 by ATM also affects p53 stabilization (Maya et al, 2001). 11331603 Pubmed 2001 ATM-dependent phosphorylation of Mdm2 on serine 395: role in p53 activation by DNA damage. Maya, R Balass, M Kim, ST Shkedy, D Leal, JF Shifman, O Moas, M Buschmann, T Ronai, Z Shiloh, Y Kastan, MB Katzir, E Oren, M Genes Dev 15:1067-77 inferred by electronic annotation IEA GO IEA Transcriptional activation of p53 responsive genes Transcriptional activation of p53 responsive genes 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> Transcriptional activation of cell cycle inhibitor p21 Transcriptional activation of cell cycle inhibitor p21 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> TP53 binds ZNF385A TP53 binds ZNF385A 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: 10250100 1 Reactome DB_ID: 10329866 1 UniProt:A0A287BFI7 ZNF385A UniProt A0A287BFI7 Reactome DB_ID: 10329868 1 p-S15,S20-TP53 Tetramer:ZNF385A [nucleoplasm] p-S15,S20-TP53 Tetramer:ZNF385A Reactome DB_ID: 10250100 1 Reactome DB_ID: 10329866 1 Reactome Database ID Release 82 10329868 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10329868 Reactome R-SSC-6803718 1 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-SSC-6803718.1 Reactome Database ID Release 82 10329870 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10329870 Reactome R-SSC-6803719 1 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-SSC-6803719.1 ZNF385A (HZF) forms a complex with TP53 (p53), interacting with the DNA binding domain of TP53. The complex of TP53 and ZNF385A associates with p53 response elements of cell cycle arrest genes, such as CDKN1A (p21) and stimulates their transcription. Under prolonged stress, ZNF385A undergoes ubiquitination and proteasome-mediated degradation, which coincides with expression of TP53-regulated pro-apoptotic genes (Das et al. 2007). 17719541 Pubmed 2007 Hzf Determines cell survival upon genotoxic stress by modulating p53 transactivation Das, Sanjeev Raj, Lakshmi Zhao, Bo Kimura, Yuki Bernstein, Alan Aaronson, Stuart A Lee, Sam W Cell 130:624-37 inferred by electronic annotation IEA GO IEA Reactome Database ID Release 82 10352220 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10352220 Reactome R-SSC-69895 1 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-SSC-69895.1 Both p53-independent and p53-dependent mechanisms of induction of p21 mRNA have been demonstrated. p21 is transcriptionally activated by p53 after DNA damage (el-Deiry et al., 1993). 8242752 Pubmed 1993 WAF1, a potential mediator of p53 tumor suppression. el-Deiry, WS Tokino, T Velculescu, VE Levy, DB Parsons, R Trent, JM Lin, D Mercer, WE Kinzler, KW Vogelstein, B Cell 75:817-25 inferred by electronic annotation IEA GO IEA Reactome Database ID Release 82 10352222 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10352222 Reactome R-SSC-69560 1 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-SSC-69560.1 p53 causes G1 arrest by inducing the expression of a cell cycle inhibitor, p21 (El-Deiry et al, 1993; Harper et al, 1993; Xiong et al, 1993). P21 binds and inactivates Cyclin-Cdk complexes that mediate G1/S progression, resulting in lack of phosphorylation of Rb, E2F sequestration and cell cycle arrest at the G1/S transition. Mice with a homozygous deletion of p21 gene are deficient in their ability to undergo a G1/S arrest in response to DNA damage (Deng et al, 1995). 8242751 Pubmed 1993 The p21 Cdk-interacting protein Cip1 is a potent inhibitor of G1 cyclin-dependent kinases. Harper, JW Adami, GR Wei, N Keyomarsi, K Elledge, SJ Cell 75:805-16 7664346 Pubmed 1995 Mice lacking p21CIP1/WAF1 undergo normal development, but are defective in G1 checkpoint control. Deng, C Zhang, P Harper, JW Elledge, SJ Leder, P Cell 82:675-84 8259214 Pubmed 1994 p21 is a universal inhibitor of cyclin kinases. Xiong, Y Hannon, GJ Zhang, H Casso, D Kobayashi, R Beach, D Nature 366:701-4 inferred by electronic annotation IEA GO IEA Inactivation of Cyclin E:Cdk2 complexes by p27/p21 Inactivation of Cyclin E:Cdk2 complexes by p27/p21 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: 10249894 1 CCNE:CDK2 [nucleoplasm] CCNE:CDK2 Reactome DB_ID: 10249418 1 UniProt:F1SPH6 UniProt F1SPH6 1 EQUAL 298 EQUAL Converted from EntitySet in Reactome Reactome DB_ID: 10249892 1 Cyclin E [nucleoplasm] Converted from EntitySet in Reactome. Each synonym is a name of a PhysicalEntity, and each XREF points to one PhysicalEntity Reactome Database ID Release 82 10249894 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10249894 Reactome R-SSC-68374 1 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-SSC-68374.1 Converted from EntitySet in Reactome Reactome DB_ID: 10250006 1 CDKN1A,CDKN1B,(CDKN1C) [nucleoplasm] Converted from EntitySet in Reactome. Each synonym is a name of a PhysicalEntity, and each XREF points to one PhysicalEntity CDKN1B [nucleoplasm] CDKN1A [nucleoplasm] UniProt Q9BDC3 UniProt F1RVT3 Reactome DB_ID: 10250056 1 Cyclin E:CDK2:CDKN1A,CDKN1B [nucleoplasm] Cyclin E:CDK2:CDKN1A,CDKN1B Reactome DB_ID: 10249894 1 Converted from EntitySet in Reactome Reactome DB_ID: 10250006 1 Reactome Database ID Release 82 10250056 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10250056 Reactome R-SSC-68376 1 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-SSC-68376.1 PHYSIOL-LEFT-TO-RIGHT ACTIVATION Converted from EntitySet in Reactome Reactome DB_ID: 10250006 GO 0004861 GO molecular function Reactome Database ID Release 82 10250057 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10250057 Reactome Database ID Release 82 10250059 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10250059 Reactome R-SSC-69562 1 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-SSC-69562.1 During 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. 16600864 Pubmed 2006 Stabilizers and destabilizers controlling cell cycle oscillators Guardavaccaro, D Pagano, Michele Mol Cell 22:1-4 16262255 Pubmed 2005 Ubiquitination of p21Cip1/WAF1 by SCFSkp2: substrate requirement and ubiquitination site selection Wang, W Nacusi, L Sheaff, RJ Liu, X Biochemistry 44:14553-64 10323868 Pubmed 1999 Ubiquitination of p27 is regulated by Cdk-dependent phosphorylation and trimeric complex formation Montagnoli, A Fiore, F Eytan, E Carrano, AC Draetta, GF Hershko, A Pagano, Michele Genes Dev 13:1181-9 inferred by electronic annotation IEA GO IEA Inactivation of Cyclin A:Cdk2 complexes by p27/p21 Inactivation of Cyclin A:Cdk2 complexes by p27/p21 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: 10262612 1 CCNA:CDK2 [nucleoplasm] CCNA:CDK2 Reactome DB_ID: 10249418 1 1 EQUAL 298 EQUAL Converted from EntitySet in Reactome Reactome DB_ID: 10249515 1 CCNA [nucleoplasm] Converted from EntitySet in Reactome. Each synonym is a name of a PhysicalEntity, and each XREF points to one PhysicalEntity Reactome Database ID Release 82 10262612 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10262612 Reactome R-SSC-141608 1 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-SSC-141608.1 Converted from EntitySet in Reactome Reactome DB_ID: 10250006 1 Reactome DB_ID: 10264260 1 Cyclin A:Cdk2:p21/p27 complex [nucleoplasm] Cyclin A:Cdk2:p21/p27 complex Reactome DB_ID: 10262612 1 Converted from EntitySet in Reactome Reactome DB_ID: 10250006 1 Reactome Database ID Release 82 10264260 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10264260 Reactome R-SSC-187926 1 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-SSC-187926.1 PHYSIOL-LEFT-TO-RIGHT ACTIVATION Converted from EntitySet in Reactome Reactome DB_ID: 10250006 Reactome Database ID Release 82 10264267 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10264267 Reactome R-SSC-187934 1 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-SSC-187934.1 During 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). 7624798 Pubmed 1995 Role of the ubiquitin-proteasome pathway in regulating abundance of the cyclin-dependent kinase inhibitor p27 Pagano, Michele Tam, SW Theodoras, AM Beer-Romero, P Del Sal, G Chau, V Yew, PR Draetta, GF Rolfe, M Science 269:682-5 inferred by electronic annotation IEA GO IEA Reactome Database ID Release 82 10349430 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10349430 Reactome R-SSC-69563 1 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-SSC-69563.1 GO 0006977 GO biological process Most of the damage-induced modifications of p53 are dependent on the ATM kinase. The first link between ATM and p53 was predicted based on the earlier studies that showed that AT cells exhibit a reduced and delayed induction of p53 following exposure to IR (Kastan et al, 1992 and Khanna and Lavin, 1993).<p>Under normal conditions, p53 is a short-lived protein. The MDM2 protein, usually interacts with p53 (Haupt et al, 1997 and Kubbutat et al, 1997), and by virtue of its E3 ubiquitin ligase activity, shuttles p53 to the cytoplasm and mediates its degradation by the ubiquitin-proteasome machinery. Upon detection of DNA damage, the ATM kinase mediates the phosphorylation of the Mdm2 protein to block its interaction with p53. Also, phosphorylation of p53 at multiple loci, by the ATM kinase and by other kinases activated by the ATM kinase, stabilizes and activates the p53 protein.<p>The p53 protein activates the transcription of cyclin-dependent kinase inhibitor, p21. p21 inactivates the CyclinE:Cdk2 complexes, and prevent entry of the cell into S phase, leading to G1 arrest. Under severe conditions, the cell may undergo apoptosis. 1423616 Pubmed 1992 A mammalian cell cycle checkpoint pathway utilizing p53 and GADD45 is defective in ataxia-telangiectasia. Kastan, MB Zhan, Q el-Deiry, WS Carrier, F Jacks, T Walsh, WV Plunkett, BS Vogelstein, B Fornace, AJ Cell 71:587-97 9153395 Pubmed 1997 Mdm2 promotes the rapid degradation of p53. Haupt, Y Maya, R Kazaz, A Oren, M Nature 387:296-9 9153396 Pubmed 1997 Regulation of p53 stability by Mdm2. Kubbutat, MH Jones, SN Vousden, KH Nature 387:299-303 8247533 Pubmed 1993 Ionizing radiation and UV induction of p53 protein by different pathways in ataxia-telangiectasia cells. Khanna, Kum Kum Lavin, MF Oncogene 8:3307-12 inferred by electronic annotation IEA GO IEA Reactome Database ID Release 82 10349432 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10349432 Reactome R-SSC-69580 1 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-SSC-69580.1 The arrest at G1/S checkpoint is mediated by the action of a widely known tumor suppressor protein, p53. Loss of p53 functions, as a result of mutations in cancer prevent the G1/S checkpoint (Kuerbitz et al, 1992). P53 is rapidly induced in response to damaged DNA. A number of kinases, phosphatases, histone acetylases and ubiquitin-conjugating enzymes regulate the stability as well as transcriptional activity of p53 after DNA damage. 1323840 Pubmed 1992 Wild-type p53 is a cell cycle checkpoint determinant following irradiation. Kuerbitz, SJ Plunkett, BS Walsh, WV Kastan, MB Proc Natl Acad Sci U S A 89:7491-5 inferred by electronic annotation IEA GO IEA