KEGG   PATHWAY: oor04115
Entry
oor04115                    Pathway                                
Name
p53 signaling pathway - Orcinus orca (killer whale)
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
oor04115  p53 signaling pathway
oor04115

Organism
Orcinus orca (killer whale) [GN:oor]
Gene
101271555  ATM; serine-protein kinase ATM isoform X1 [KO:K04728] [EC:2.7.11.1]
101289528  CHEK2; serine/threonine-protein kinase Chk2 isoform X2 [KO:K06641] [EC:2.7.11.1]
101282923  ATR; serine/threonine-protein kinase ATR isoform X2 [KO:K06640] [EC:2.7.11.1]
101270160  CHEK1; serine/threonine-protein kinase Chk1 isoform X1 [KO:K02216] [EC:2.7.11.1]
101289636  GORAB; RAB6-interacting golgin isoform X1 [KO:K19748]
101276268  cyclin-dependent kinase inhibitor 2A isoform X1 [KO:K06621]
101286234  MDM2; E3 ubiquitin-protein ligase Mdm2 isoform X1 [KO:K06643] [EC:2.3.2.27]
101282024  MDM4; protein Mdm4 isoform X1 [KO:K10127]
101285670  TP53; cellular tumor antigen p53 isoform X2 [KO:K04451]
101287466  PPP1R13L; relA-associated inhibitor [KO:K27356]
101288384  CDKN1A; cyclin-dependent kinase inhibitor 1 [KO:K06625]
101273294  CCND1; G1/S-specific cyclin-D1 isoform X2 [KO:K04503]
101274693  CCND2; G1/S-specific cyclin-D2 [KO:K10151]
101274576  CCND3; G1/S-specific cyclin-D3 isoform X1 [KO:K10152]
101283760  CDK4; cyclin-dependent kinase 4 isoform X1 [KO:K02089] [EC:2.7.11.22]
101271733  CDK6; cyclin-dependent kinase 6 [KO:K02091] [EC:2.7.11.22]
101285614  CCNE2; G1/S-specific cyclin-E2 isoform X1 [KO:K06626]
101272657  CCNE1; G1/S-specific cyclin-E1 [KO:K06626]
101289729  CDK2; cyclin-dependent kinase 2 isoform X2 [KO:K02206] [EC:2.7.11.22]
101274324  SFN; 14-3-3 protein sigma [KO:K06644]
101289828  RPRM; protein reprimo [KO:K10128]
101286536  CCNB1; G2/mitotic-specific cyclin-B1 [KO:K05868]
101277999  CCNB2; G2/mitotic-specific cyclin-B2 isoform X1 [KO:K21770]
101271295  CDK1; cyclin-dependent kinase 1 isoform X2 [KO:K02087] [EC:2.7.11.22 2.7.11.23]
101281934  GADD45A; growth arrest and DNA damage-inducible protein GADD45 alpha [KO:K04402]
101281489  GADD45G; growth arrest and DNA damage-inducible protein GADD45 gamma [KO:K04402]
101285919  GADD45B; growth arrest and DNA damage-inducible protein GADD45 beta isoform X1 [KO:K04402]
101278926  GTSE1; G2 and S phase-expressed protein 1 isoform X1 [KO:K10129]
101275605  ZNF385A; zinc finger protein 385A isoform X1 [KO:K26543]
101284022  FAS; tumor necrosis factor receptor superfamily member 6 isoform X5 [KO:K04390]
101284188  PIDD1; p53-induced death domain-containing protein 1 isoform X1 [KO:K10130]
101271509  tumor necrosis factor receptor superfamily member 10A isoform X9 [KO:K04722]
101281780  CASP8; caspase-8 isoform X1 [KO:K04398] [EC:3.4.22.61]
101277745  BID; BH3-interacting domain death agonist isoform X1 [KO:K04726]
101285349  BAX; apoptosis regulator BAX isoform X1 [KO:K02159]
101269536  PMAIP1; phorbol-12-myristate-13-acetate-induced protein 1 [KO:K10131]
101275681  BBC3; bcl-2-binding component 3 isoform X4 [KO:K10132]
101273058  SIVA1; apoptosis regulatory protein Siva isoform X1 [KO:K22744]
101288063  BCL2L1; bcl-2-like protein 1 isoform X1 [KO:K04570]
101276750  BCL2; apoptosis regulator Bcl-2 [KO:K02161]
101272745  TP53I3; LOW QUALITY PROTEIN: quinone oxidoreductase PIG3 [KO:K10133] [EC:1.-.-.-]
101290495  EI24; etoposide-induced protein 2.4 homolog isoform X1 [KO:K10134]
101281755  LOW QUALITY PROTEIN: etoposide-induced protein 2.4 homolog [KO:K10134]
101281633  SHISA5; protein shisa-5 isoform X1 [KO:K10135]
101285135  PERP; p53 apoptosis effector related to PMP-22 [KO:K10136]
101278324  ZMAT3; zinc finger matrin-type protein 3 isoform X1 [KO:K10137]
101289867  SIAH1; E3 ubiquitin-protein ligase SIAH1 isoform X1 [KO:K04506] [EC:2.3.2.27]
105747906  cytochrome c-like [KO:K08738]
101283052  cytochrome c [KO:K08738]
101275631  cytochrome c-like [KO:K08738]
105747703  cytochrome c 2 [KO:K08738]
101272869  cytochrome c-like [KO:K08738]
117203203  LOW QUALITY PROTEIN: cytochrome c-like [KO:K08738]
101280303  APAF1; apoptotic protease-activating factor 1 isoform X4 [KO:K02084]
101271677  CASP9; caspase-9 isoform X1 [KO:K04399] [EC:3.4.22.62]
101289847  CASP3; caspase-3 isoform X2 [KO:K02187] [EC:3.4.22.56]
101269994  AIFM2; ferroptosis suppressor protein 1 isoform X4 [KO:K22745]
101272404  IGFBP3; insulin-like growth factor-binding protein 3 [KO:K10138]
101269950  IGF1; insulin-like growth factor I isoform X2 [KO:K05459]
101273613  SERPINE1; plasminogen activator inhibitor 1 [KO:K03982]
101274491  ADGRB1; adhesion G protein-coupled receptor B1 isoform X1 [KO:K04596]
101281704  CD82; CD82 antigen isoform X1 [KO:K06509]
101283920  THBS1; thrombospondin-1 [KO:K16857]
101277821  SERPINB5; serpin B5 [KO:K10139]
101270094  DDB2; DNA damage-binding protein 2 [KO:K10140]
101273644  RRM2B; ribonucleoside-diphosphate reductase subunit M2 B isoform X1 [KO:K10808] [EC:1.17.4.1]
101270798  RRM2; ribonucleoside-diphosphate reductase subunit M2 isoform X4 [KO:K10808] [EC:1.17.4.1]
105748332  LOW QUALITY PROTEIN: ribonucleoside-diphosphate reductase subunit M2-like [KO:K10808] [EC:1.17.4.1]
101272574  SESN3; sestrin-3 isoform X2 [KO:K10141]
101287521  SESN1; sestrin-1 isoform X2 [KO:K10141]
101286950  SESN2; sestrin-2 [KO:K20394]
101289838  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]
101276336  TSC2; tuberin isoform X9 [KO:K07207]
101287237  STEAP3; metalloreductase STEAP3 isoform X1 [KO:K10142] [EC:1.16.1.-]
101278717  COP1; E3 ubiquitin-protein ligase COP1 isoform X1 [KO:K10143] [EC:2.3.2.27]
101270901  RCHY1; LOW QUALITY PROTEIN: RING finger and CHY zinc finger domain-containing protein 1 [KO:K10144] [EC:2.3.2.27]
101280307  LOW QUALITY PROTEIN: RING finger and CHY zinc finger domain-containing protein 1-like [KO:K10144] [EC:2.3.2.27]
101288558  CCNG1; cyclin-G1 [KO:K10145]
125965380  cyclin-G1-like isoform X1 [KO:K10145]
101285375  CCNG2; cyclin-G2 isoform X1 [KO:K10146]
101280576  PPM1D; protein phosphatase 1D [KO:K10147] [EC:3.1.3.16]
101287226  TP73; tumor protein p73 isoform X2 [KO:K10148]
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
oor04110  Cell cycle
oor04210  Apoptosis
oor04218  Cellular senescence
KO pathway
ko04115   
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