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

Disease
H00409  Type 2 diabetes mellitus
H00881  Li-Fraumeni syndrome
H00896  Lymphangioleiomyomatosis
H00915  Tuberous sclerosis complex
H00992  Seckel syndrome
H01007  Choroid plexus papilloma
H01106  Plasminogen activator inhibitor type 1 deficiency
H01195  VACTERL/VATER association
Orthology
K04728  serine-protein kinase ATM [EC:2.7.11.1]
K06641  serine/threonine-protein kinase CHEK2 [EC:2.7.11.1]
K06640  serine/threonine-protein kinase ATR [EC:2.7.11.1]
K02216  serine/threonine-protein kinase CHEK1 [EC:2.7.11.1]
K19748  RAB6-interacting golgin
K06621  cyclin-dependent kinase inhibitor 2A
K06643  E3 ubiquitin-protein ligase Mdm2 [EC:2.3.2.27]
K10127  protein Mdm4
K04451  tumor protein p53
K06625  cyclin-dependent kinase inhibitor 1A
K04503  G1/S-specific cyclin-D1
K10151  G1/S-specific cyclin-D2
K10152  G1/S-specific cyclin-D3
K02089  cyclin-dependent kinase 4 [EC:2.7.11.22]
K02091  cyclin-dependent kinase 6 [EC:2.7.11.22]
K06626  G1/S-specific cyclin-E1
K02206  cyclin-dependent kinase 2 [EC:2.7.11.22]
K06644  stratifin
K10128  reprimo, TP53-dependent G2 arrest mediator candidate
K05868  G2/mitotic-specific cyclin-B1
K21770  G2/mitotic-specific cyclin-B2
K02087  cyclin-dependent kinase 1 [EC:2.7.11.22 2.7.11.23]
K04402  growth arrest and DNA-damage-inducible protein
K10129  G-2 and S-phase expressed protein 1
K04390  tumor necrosis factor receptor superfamily member 6
K10130  leucine-rich repeats and death domain-containing protein
K04722  tumor necrosis factor receptor superfamily member 10A/B
K04398  caspase 8 [EC:3.4.22.61]
K04726  BH3 interacting domain death agonist
K02159  apoptosis regulator BAX
K10131  phorbol-12-myristate-13-acetate-induced protein 1
K10132  Bcl-2-binding component 3
K13773  p53-regulated apoptosis-inducing protein 1
K22744  apoptosis regulatory protein Siva
K04570  Bcl-2-like 1 (apoptosis regulator Bcl-X)
K02161  apoptosis regulator Bcl-2
K10133  tumor protein p53-inducible protein 3 [EC:1.-.-.-]
K10134  etoposide-induced 2.4 mRNA
K10135  scotin
K10136  TP53 apoptosis effector
K10137  zinc finger, matrin type 3
K04506  E3 ubiquitin-protein ligase SIAH1 [EC:2.3.2.27]
K08738  cytochrome c
K02084  apoptotic protease-activating factor
K04399  caspase 9 [EC:3.4.22.62]
K02187  caspase 3 [EC:3.4.22.56]
K22745  apoptosis-inducing factor 2
K10138  insulin-like growth factor-binding protein 3
K05459  insulin-like growth factor 1
K03982  plasminogen activator inhibitor 1
K04596  adhesion G protein-coupled receptor B1
K06509  CD82 antigen
K16857  thrombospondin 1
K10139  serpin B5
K10140  DNA damage-binding protein 2
K10808  ribonucleoside-diphosphate reductase subunit M2 [EC:1.17.4.1]
K10141  sestrin 1/3
K20394  sestrin 2
K01110  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]
K07207  tuberous sclerosis 2
K10142  metalloreductase STEAP3 [EC:1.16.1.-]
K10143  E3 ubiquitin-protein ligase RFWD2 [EC:2.3.2.27]
K10144  RING finger and CHY zinc finger domain-containing protein 1 [EC:2.3.2.27]
K10145  cyclin G1
K10146  cyclin G2
K10147  protein phosphatase 1D [EC:3.1.3.16]
K10148  tumor protein p73
Reference
  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
  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
  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
  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
  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
  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
  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
  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
  Authors
Sherr CJ.
  Title
Divorcing ARF and p53: an unsettled case.
  Journal
Nat Rev Cancer 6:663-73 (2006)
DOI:10.1038/nrc1954
Reference
  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
  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
  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
  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
  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
Related
pathway
ko04110  Cell cycle
ko04210  Apoptosis
ko04218  Cellular senescence
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