KEGG   PATHWAY: rno04115
Entry
rno04115                    Pathway                                
Name
p53 signaling pathway - Rattus norvegicus (rat)
Description
p53 activation is induced by a number of stress signals, including DNA damage, oxidative stress and activated oncogenes. The p53 protein is employed as a transcriptional activator of p53-regulated genes. This results in three major outputs; cell cycle arrest, cellular senescence or apoptosis. Other p53-regulated gene functions communicate with adjacent cells, repair the damaged DNA or set up positive and negative feedback loops that enhance or attenuate the functions of the p53 protein and integrate these stress responses with other signal transduction pathways.
Class
Cellular Processes; Cell growth and death
Pathway map
rno04115  p53 signaling pathway
rno04115

Organism
Rattus norvegicus (rat) [GN:rno]
Gene
100359539  Rrm2l1; ribonucleoside-diphosphate reductase subunit M2-like [KO:K10808] [EC:1.17.4.1]
100362121  Ddb2; DNA damage-binding protein 2 [KO:K10140]
103690862  [KO:K06644]
114212  Chek2; serine/threonine-protein kinase Chk2 [KO:K06641] [EC:2.7.11.1]
114483  Cdk6; cyclin-dependent kinase 6 [KO:K02091] [EC:2.7.11.22]
114851  Cdkn1a; cyclin-dependent kinase inhibitor 1 [KO:K06625]
116589  Serpinb5; serpin B5 [KO:K10139]
120099910  [KO:K08738]
140583  Chek1; serine/threonine-protein kinase Chk1 [KO:K02216] [EC:2.7.11.1]
140941  Siah1; E3 ubiquitin-protein ligase SIAH1 [KO:K04506] [EC:2.3.2.27]
170824  Steap3; metalloreductase STEAP3 [KO:K10142] [EC:1.16.1.-]
24224  Bcl2; apoptosis regulator Bcl-2 [KO:K02161]
24482  Igf1; insulin-like growth factor I isoform d preproprotein [KO:K05459]
24484  Igfbp3; insulin-like growth factor-binding protein 3 precursor [KO:K10138]
246097  Fas; tumor necrosis factor receptor superfamily member 6 precursor [KO:K04390]
24617  Serpine1; plasminogen activator inhibitor 1 precursor [KO:K03982]
24842  Tp53; cellular tumor antigen p53 [KO:K04451]
24855  Tsc2; tuberin [KO:K07207]
24887  Bax; apoptosis regulator BAX [KO:K02159]
24888  Bcl2l1; bcl-2-like protein 1 isoform 2 [KO:K04570]
25112  Gadd45a; growth arrest and DNA damage-inducible protein GADD45 alpha [KO:K04402]
25163  Cdkn2a; cyclin-dependent kinase inhibitor 2A [KO:K06621]
25193  Ccnd3; G1/S-specific cyclin-D3 [KO:K10152]
25203  Ccnb1; G2/mitotic-specific cyclin-B1 [KO:K05868]
25309  Cycs; cytochrome c, somatic [KO:K08738]
25310  Cyct; cytochrome c, testis-specific [KO:K08738]
25402  Casp3; caspase-3 [KO:K02187] [EC:3.4.22.56]
25405  Ccng1; cyclin-G1 [KO:K10145]
25729  Ccne1; G1/S-specific cyclin-E1 [KO:K06626]
287585  Ppm1d; protein phosphatase 1D [KO:K10147] [EC:3.1.3.16]
289508  Rchy1; RING finger and CHY zinc finger domain-containing protein 1 [KO:K10144] [EC:2.3.2.27]
290019  Cycsl3; cytochrome c, somatic-like [KO:K08738]
291005  Gadd45g; growth arrest and DNA damage-inducible protein GADD45 gamma [KO:K04402]
29157  Ccng2; cyclin-G2 [KO:K10146]
292949  Perp; p53 apoptosis effector related to PMP-22 [KO:K10136]
293625  Pidd1; p53-induced death domain-containing protein 1 [KO:K10130]
294518  Sesn1; sestrin-1 [KO:K10141]
298795  Sfnl1; stratifin like 1 [KO:K06644]
299626  Gadd45b; growth arrest and DNA damage-inducible protein GADD45 beta [KO:K04402]
299976  Rrm2b; ribonucleoside-diphosphate reductase subunit M2 B [KO:K10808] [EC:1.17.4.1]
300126  Gtse1; G2 and S phase-expressed protein 1 [KO:K10129]
300514  Ei24; etoposide-induced protein 2.4 homolog [KO:K10134]
300711  Atm; serine-protein kinase ATM [KO:K04728] [EC:2.7.11.1]
301013  Shisa5; protein shisa-5 isoform 4 [KO:K10135]
304798  Mdm4; protein Mdm4 [KO:K10127]
304923  Gorab; RAB6-interacting golgin [KO:K19748]
313017  Sfn; 14-3-3 protein sigma [KO:K06644]
314856  Mdm2; E3 ubiquitin-protein ligase Mdm2 [KO:K06643] [EC:2.3.2.27]
315427  Sesn3; sestrin-3 [KO:K10141]
317673  Bbc3; bcl-2-binding component 3 [KO:K10132]
360860  Cop1; E3 ubiquitin-protein ligase COP1 [KO:K10143] [EC:2.3.2.27]
361843  Aifm2; ferroptosis suppressor protein 1 [KO:K22745]
362485  Ccne2; G1/S-specific cyclin-E2 [KO:K06626]
362675  Tp73; tumor protein p73 [KO:K10148]
362720  Rrm2; ribonucleoside-diphosphate reductase subunit M2 [KO:K10808] [EC:1.17.4.1]
362791  Siva1; apoptosis regulatory protein Siva [KO:K22744]
362817  Cdk2; cyclin-dependent kinase 2 [KO:K02206] [EC:2.7.11.22]
362931  Adgrb1; adhesion G protein-coupled receptor B1 precursor [KO:K04596]
363088  Ccnb2; G2/mitotic-specific cyclin-B2 [KO:K21770]
367149  Bax-ps1; apoptosis regulator BAX-like [KO:K02159]
445442  Thbs1; thrombospondin-1 isoform 1 precursor [KO:K16857]
492821  Pmaip1; phorbol-12-myristate-13-acetate-induced protein 1 [KO:K10131]
502988  Sesn2; sestrin-2 [KO:K20394]
50557  Pten; phosphatidylinositol 3,4,5-trisphosphate 3-phosphatase and dual-specificity protein phosphatase PTEN [KO:K01110] [EC:3.1.3.16 3.1.3.48 3.1.3.67]
54237  Cdk1; cyclin-dependent kinase 1 [KO:K02087] [EC:2.7.11.22 2.7.11.23]
58918  Casp9; caspase-9 [KO:K04399] [EC:3.4.22.62]
58919  Ccnd1; G1/S-specific cyclin-D1 [KO:K04503]
64033  Ccnd2; G1/S-specific cyclin-D2 [KO:K10151]
64044  Casp8; caspase-8 [KO:K04398] [EC:3.4.22.61]
64394  Zmat3; zinc finger matrin-type protein 3 [KO:K10137]
64625  Bid; BH3-interacting domain death agonist [KO:K04726]
679794  Cycsl1; cytochrome c, somatic-like [KO:K08738]
680110  Rprm; protein reprimo [KO:K10128]
681314  [KO:K02159]
685055  Atr; serine/threonine-protein kinase ATR [KO:K06640] [EC:2.7.11.1]
685474  Zfp385a; zinc finger protein 385A isoform 2 [KO:K26543]
686781  Ppp1r13l; protein phosphatase 1, regulatory subunit 13 like [KO:K27356]
690675  Cycsl2; cytochrome c, somatic-like [KO:K08738]
78963  Apaf1; apoptotic protease-activating factor 1 [KO:K02084]
83628  Cd82; CD82 antigen [KO:K06509]
94201  Cdk4; cyclin-dependent kinase 4 isoform 1 [KO:K02089] [EC:2.7.11.22]
Reference
PMID:16557269
  Authors
Levine AJ, Hu W, Feng Z.
  Title
The P53 pathway: what questions remain to be explored?
  Journal
Cell Death Differ 13:1027-36 (2006)
DOI:10.1038/sj.cdd.4401910
Reference
PMID:15838523
  Authors
Harris SL, Levine AJ.
  Title
The p53 pathway: positive and negative feedback loops.
  Journal
Oncogene 24:2899-908 (2005)
DOI:10.1038/sj.onc.1208615
Reference
PMID:11747320
  Authors
Balint E E, Vousden KH.
  Title
Activation and activities of the p53 tumour suppressor protein.
  Journal
Br J Cancer 85:1813-23 (2001)
DOI:10.1054/bjoc.2001.2128
Reference
PMID:11313928
  Authors
Taylor WR, Stark GR.
  Title
Regulation of the G2/M transition by p53.
  Journal
Oncogene 20:1803-15 (2001)
DOI:10.1038/sj.onc.1204252
Reference
PMID:15116721
  Authors
Hofseth LJ, Hussain SP, Harris CC.
  Title
p53: 25 years after its discovery.
  Journal
Trends Pharmacol Sci 25:177-81 (2004)
DOI:10.1016/j.tips.2004.02.009
Reference
PMID:12505356
  Authors
Pietenpol JA, Stewart ZA.
  Title
Cell cycle checkpoint signaling: cell cycle arrest versus apoptosis.
  Journal
Toxicology 181-182:475-81 (2002)
DOI:10.1016/S0300-483X(02)00460-2
Reference
PMID:10714958
  Authors
Tokino T, Nakamura Y.
  Title
The role of p53-target genes in human cancer.
  Journal
Crit Rev Oncol Hematol 33:1-6 (2000)
DOI:10.1016/S1040-8428(99)00051-7
Reference
PMID:16697662
  Authors
Hermeking H, Benzinger A.
  Title
14-3-3 proteins in cell cycle regulation.
  Journal
Semin Cancer Biol 16:183-92 (2006)
DOI:10.1016/j.semcancer.2006.03.002
Reference
PMID:16915296
  Authors
Sherr CJ.
  Title
Divorcing ARF and p53: an unsettled case.
  Journal
Nat Rev Cancer 6:663-73 (2006)
DOI:10.1038/nrc1954
Reference
PMID:17409411
  Authors
Feng Z, Hu W, de Stanchina E, Teresky AK, Jin S, Lowe S, Levine AJ.
  Title
The 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 pathways.
  Journal
Cancer Res 67:3043-53 (2007)
DOI:10.1158/0008-5472.CAN-06-4149
Reference
PMID:26037915
  Authors
Resnick-Silverman L, Manfredi JJ
  Title
Two Faces of SIVA.
  Journal
Cancer Discov 5:581-3 (2015)
DOI:10.1158/2159-8290.CD-15-0484
Reference
PMID:19584092
  Authors
Resch U, Schichl YM, Winsauer G, Gudi R, Prasad K, de Martin R
  Title
Siva1 is a XIAP-interacting protein that balances NFkappaB and JNK signalling to promote apoptosis.
  Journal
J Cell Sci 122:2651-61 (2009)
DOI:10.1242/jcs.049940
Reference
PMID:19240372
  Authors
Barkinge JL, Gudi R, Sarah H, Chu F, Borthakur A, Prabhakar BS, Prasad KV
  Title
The p53-induced Siva-1 plays a significant role in cisplatin-mediated apoptosis.
  Journal
J Carcinog 8:2 (2009)
DOI:10.4103/1477-3163.45389
Reference
PMID:12135761
  Authors
Ohiro Y, Garkavtsev I, Kobayashi S, Sreekumar KR, Nantz R, Higashikubo BT, Duffy SL, Higashikubo R, Usheva A, Gius D, Kley N, Horikoshi N
  Title
A novel p53-inducible apoptogenic gene, PRG3, encodes a homologue of the apoptosis-inducing factor (AIF).
  Journal
FEBS Lett 524:163-71 (2002)
DOI:10.1016/S0014-5793(02)03049-1
Reference
PMID:26646590
  Authors
Hu Y, Ge W, Wang X, Sutendra G, Zhao K, Dedeic Z, Slee EA, Baer C, Lu X
  Title
Caspase cleavage of iASPP potentiates its ability to inhibit p53 and NF-kappaB.
  Journal
Oncotarget 6:42478-90 (2015)
DOI:10.18632/oncotarget.6478
Related
pathway
rno04110  Cell cycle
rno04210  Apoptosis
rno04218  Cellular senescence
KO pathway
ko04115   

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