KEGG   PATHWAY: ko04115
Entry
ko04115                     Pathway                                
Name
p53 signaling pathway
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
ko04115  p53 signaling pathway
ko04115

Orthology
K01110  PTEN; phosphatidylinositol-3,4,5-trisphosphate 3-phosphatase and dual-specificity protein phosphatase PTEN [EC:3.1.3.16 3.1.3.48 3.1.3.67]
K02084  APAF1; apoptotic protease-activating factor
K02087  CDK1, CDC2; cyclin-dependent kinase 1 [EC:2.7.11.22 2.7.11.23]
K02089  CDK4; cyclin-dependent kinase 4 [EC:2.7.11.22]
K02091  CDK6; cyclin-dependent kinase 6 [EC:2.7.11.22]
K02159  BAX; apoptosis regulator BAX
K02161  BCL2; apoptosis regulator Bcl-2
K02187  CASP3; caspase 3 [EC:3.4.22.56]
K02206  CDK2; cyclin-dependent kinase 2 [EC:2.7.11.22]
K02216  CHEK1; serine/threonine-protein kinase CHEK1 [EC:2.7.11.1]
K03982  SERPINE1, PAI1; plasminogen activator inhibitor 1
K04390  TNFRSF6, FAS, CD95; tumor necrosis factor receptor superfamily member 6
K04398  CASP8; caspase 8 [EC:3.4.22.61]
K04399  CASP9; caspase 9 [EC:3.4.22.62]
K04402  GADD45; growth arrest and DNA-damage-inducible protein
K04451  TP53, P53; tumor protein p53
K04503  CCND1; G1/S-specific cyclin-D1
K04506  SIAH1; E3 ubiquitin-protein ligase SIAH1 [EC:2.3.2.27]
K04570  BCL2L1, bcl-xL; Bcl-2-like 1 (apoptosis regulator Bcl-X)
K04596  ADGRB1, BAI1; adhesion G protein-coupled receptor B1
K04722  TNFRSF10A_B, TRAILR1_2, DR4_5, CD261_2; tumor necrosis factor receptor superfamily member 10A/B
K04726  BID; BH3 interacting domain death agonist
K04728  ATM, TEL1; serine-protein kinase ATM [EC:2.7.11.1]
K05459  IGF1; insulin-like growth factor 1
K05868  CCNB1; G2/mitotic-specific cyclin-B1
K06509  KAI1, CD82, TSPAN27; CD82 antigen
K06621  CDKN2A, P16, INK4A; cyclin-dependent kinase inhibitor 2A
K06625  CDKN1A, P21, CIP1; cyclin-dependent kinase inhibitor 1A
K06626  CCNE; G1/S-specific cyclin-E1
K06640  ATR; serine/threonine-protein kinase ATR [EC:2.7.11.1]
K06641  CHEK2; serine/threonine-protein kinase CHEK2 [EC:2.7.11.1]
K06643  MDM2; E3 ubiquitin-protein ligase Mdm2 [EC:2.3.2.27]
K06644  SFN; stratifin
K07207  TSC2; tuberous sclerosis 2
K08738  CYC; cytochrome c
K10127  MDM4, MDMX; protein Mdm4
K10128  RPRM; reprimo, TP53-dependent G2 arrest mediator candidate
K10129  GTSE1, B99; G-2 and S-phase expressed protein 1
K10130  LRDD, PIDD; leucine-rich repeats and death domain-containing protein
K10131  PMAIP1, NOXA; phorbol-12-myristate-13-acetate-induced protein 1
K10132  BBC3, PUMA; Bcl-2-binding component 3
K10133  TP53I3; tumor protein p53-inducible protein 3 [EC:1.-.-.-]
K10134  EI24; etoposide-induced 2.4 mRNA
K10135  SCOTIN; scotin
K10136  PERP; TP53 apoptosis effector
K10137  ZMAT3; zinc finger, matrin type 3
K10138  IGFBP3; insulin-like growth factor-binding protein 3
K10139  SERPINB5; serpin B5
K10140  DDB2; DNA damage-binding protein 2
K10141  SESN1_3; sestrin 1/3
K10142  STEAP3, TSAP6; metalloreductase STEAP3 [EC:1.16.1.-]
K10143  RFWD2, COP1; E3 ubiquitin-protein ligase RFWD2 [EC:2.3.2.27]
K10144  RCHY1, PIRH2; RING finger and CHY zinc finger domain-containing protein 1 [EC:2.3.2.27]
K10145  CCNG1; cyclin G1
K10146  CCNG2; cyclin G2
K10147  PPM1D, WIP1; protein phosphatase 1D [EC:3.1.3.16]
K10148  TP73; tumor protein p73
K10151  CCND2; G1/S-specific cyclin-D2
K10152  CCND3; G1/S-specific cyclin-D3
K10808  RRM2; ribonucleoside-diphosphate reductase subunit M2 [EC:1.17.4.1]
K13773  TP53AIP1; p53-regulated apoptosis-inducing protein 1
K16857  THBS1; thrombospondin 1
K19748  GORAB, SCYL1BP1; RAB6-interacting golgin
K20394  SESN2; sestrin 2
K21770  CCNB2; G2/mitotic-specific cyclin-B2
K22744  SIVA1; apoptosis regulatory protein Siva
K22745  AIFM2; apoptosis-inducing factor 2
K26543  ZNF385A, HZF; zinc finger protein 385A
K27356  PPP1R13L; RelA-associated inhibitor
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
ko04110  Cell cycle
ko04210  Apoptosis
ko04218  Cellular senescence

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