KEGG   PATHWAY: hsa04115Help
Entry
hsa04115                    Pathway                                

Name
p53 signaling pathway - Homo sapiens (human)
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
BRITE hierarchy
Pathway map
p53 signaling pathway
hsa04115

All organismsOrtholog table
Disease
H00409  
Type II diabetes mellitus
H00848  
Ataxia with ocular apraxia (AOA)
H00881  
Li-Fraumeni syndrome
H00896  
Lymphangioleiomyomatosis (LAM)
H00915  
Tuberous sclerosis complex (TSC)
H00992  
Seckel syndrome
H01007  
Choroid plexus papilloma
H01106  
Plasminogen activator inhibitor type 1 (PAI-1) deficiency
H01195  
VACTERL/VATER association
Drug
D00341  
Hydroxycarbamide (JAN/INN)
D06611  
Lexatumumab (USAN/INN)
D08656  
Aleplasinin (USAN/INN)
D08887  
Cenersen sodium (USAN)
D09329  
Conatumumab (USAN/INN)
D09604  
Dinaciclib (USAN/INN)
D09888  
Drozitumab (USAN/INN)
D10372  
Palbociclib (USAN)
Organism
Homo sapiens (human) [GN:hsa]
Gene
472  
ATM; ataxia telangiectasia mutated [KO:K04728] [EC:2.7.11.1]
11200  
CHEK2; checkpoint kinase 2 [KO:K06641] [EC:2.7.11.1]
545  
ATR; ataxia telangiectasia and Rad3 related [KO:K06640] [EC:2.7.11.1]
1111  
CHEK1; checkpoint kinase 1 [KO:K02216] [EC:2.7.11.1]
1029  
CDKN2A; cyclin-dependent kinase inhibitor 2A [KO:K06621]
4193  
MDM2; MDM2 oncogene, E3 ubiquitin protein ligase [KO:K06643] [EC:6.3.2.19]
4194  
MDM4; MDM4, p53 regulator [KO:K10127]
7157  
TP53; tumor protein p53 [KO:K04451]
1026  
CDKN1A; cyclin-dependent kinase inhibitor 1A (p21, Cip1) [KO:K06625]
595  
CCND1; cyclin D1 [KO:K04503]
894  
CCND2; cyclin D2 [KO:K10151]
896  
CCND3; cyclin D3 [KO:K10152]
1019  
CDK4; cyclin-dependent kinase 4 [KO:K02089] [EC:2.7.11.22]
1021  
CDK6; cyclin-dependent kinase 6 [KO:K02091] [EC:2.7.11.22]
898  
CCNE1; cyclin E1 [KO:K06626]
9134  
CCNE2; cyclin E2 [KO:K06626]
1017  
CDK2; cyclin-dependent kinase 2 [KO:K02206] [EC:2.7.11.22]
2810  
SFN; stratifin [KO:K06644]
56475  
RPRM; reprimo, TP53 dependent G2 arrest mediator candidate [KO:K10128]
891  
CCNB1; cyclin B1 [KO:K05868]
9133  
CCNB2; cyclin B2 [KO:K05868]
85417  
CCNB3; cyclin B3 [KO:K05868]
983  
CDK1; cyclin-dependent kinase 1 [KO:K02087] [EC:2.7.11.23 2.7.11.22]
1647  
GADD45A; growth arrest and DNA-damage-inducible, alpha [KO:K04402]
4616  
GADD45B; growth arrest and DNA-damage-inducible, beta [KO:K04402]
10912  
GADD45G; growth arrest and DNA-damage-inducible, gamma [KO:K04402]
51512  
GTSE1; G-2 and S-phase expressed 1 [KO:K10129]
355  
FAS; Fas cell surface death receptor [KO:K04390]
55367  
PIDD1; p53-induced death domain protein 1 [KO:K10130]
841  
CASP8; caspase 8, apoptosis-related cysteine peptidase [KO:K04398] [EC:3.4.22.61]
637  
BID; BH3 interacting domain death agonist [KO:K04726]
581  
BAX; BCL2-associated X protein [KO:K02159]
5366  
PMAIP1; phorbol-12-myristate-13-acetate-induced protein 1 [KO:K10131]
27113  
BBC3; BCL2 binding component 3 [KO:K10132]
63970  
TP53AIP1; tumor protein p53 regulated apoptosis inducing protein 1 [KO:K13773]
9540  
TP53I3; tumor protein p53 inducible protein 3 [KO:K10133] [EC:1.-.-.-]
9538  
EI24; etoposide induced 2.4 [KO:K10134]
51246  
SHISA5; shisa family member 5 [KO:K10135]
64065  
PERP; PERP, TP53 apoptosis effector [KO:K10136]
64393  
ZMAT3; zinc finger, matrin-type 3 [KO:K10137]
6477  
SIAH1; siah E3 ubiquitin protein ligase 1 [KO:K04506] [EC:6.3.2.19]
54205  
CYCS; cytochrome c, somatic [KO:K08738]
317  
APAF1; apoptotic peptidase activating factor 1 [KO:K02084]
842  
CASP9; caspase 9, apoptosis-related cysteine peptidase [KO:K04399] [EC:3.4.22.62]
836  
CASP3; caspase 3, apoptosis-related cysteine peptidase [KO:K02187] [EC:3.4.22.56]
3486  
IGFBP3; insulin-like growth factor binding protein 3 [KO:K10138]
3479  
IGF1; insulin-like growth factor 1 (somatomedin C) [KO:K05459]
5054  
SERPINE1; serpin peptidase inhibitor, clade E (nexin, plasminogen activator inhibitor type 1), member 1 [KO:K03982]
575  
BAI1; brain-specific angiogenesis inhibitor 1 [KO:K04596]
3732  
CD82; CD82 molecule [KO:K06509]
7057  
THBS1; thrombospondin 1 [KO:K16857]
5268  
SERPINB5; serpin peptidase inhibitor, clade B (ovalbumin), member 5 [KO:K10139]
1643  
DDB2; damage-specific DNA binding protein 2, 48kDa [KO:K10140]
50484  
RRM2B; ribonucleotide reductase M2 B (TP53 inducible) [KO:K10808] [EC:1.17.4.1]
6241  
RRM2; ribonucleotide reductase M2 [KO:K10808] [EC:1.17.4.1]
27244  
SESN1; sestrin 1 [KO:K10141]
83667  
SESN2; sestrin 2 [KO:K10141]
143686  
SESN3; sestrin 3 [KO:K10141]
5728  
PTEN; phosphatase and tensin homolog [KO:K01110] [EC:3.1.3.67 3.1.3.48 3.1.3.16]
7249  
TSC2; tuberous sclerosis 2 [KO:K07207]
55240  
STEAP3; STEAP family member 3, metalloreductase [KO:K10142] [EC:1.16.1.-]
64326  
RFWD2; ring finger and WD repeat domain 2, E3 ubiquitin protein ligase [KO:K10143] [EC:6.3.2.19]
25898  
RCHY1; ring finger and CHY zinc finger domain containing 1, E3 ubiquitin protein ligase [KO:K10144] [EC:6.3.2.19]
900  
CCNG1; cyclin G1 [KO:K10145]
901  
CCNG2; cyclin G2 [KO:K10146]
8493  
PPM1D; protein phosphatase, Mg2+/Mn2+ dependent, 1D [KO:K10147] [EC:3.1.3.16]
7161  
TP73; tumor protein p73 [KO:K10148]
8795  
TNFRSF10B; tumor necrosis factor receptor superfamily, member 10b [KO:K04722]
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)
Reference
  Authors
Harris SL, Levine AJ.
  Title
The p53 pathway: positive and negative feedback loops.
  Journal
Oncogene 24:2899-908 (2005)
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)
Reference
  Authors
Taylor WR, Stark GR.
  Title
Regulation of the G2/M transition by p53.
  Journal
Oncogene 20:1803-15 (2001)
Reference
  Authors
Hofseth LJ, Hussain SP, Harris CC.
  Title
p53: 25 years after its discovery.
  Journal
Trends Pharmacol Sci 25:177-81 (2004)
Reference
  Authors
Pietenpol JA, Stewart ZA.
  Title
Cell cycle checkpoint signaling: cell cycle arrest versus apoptosis.
  Journal
Toxicology 181-182:475-81 (2002)
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)
Reference
  Authors
Hermeking H, Benzinger A.
  Title
14-3-3 proteins in cell cycle regulation.
  Journal
Semin Cancer Biol 16:183-92 (2006)
Reference
  Authors
Sherr CJ.
  Title
Divorcing ARF and p53: an unsettled case.
  Journal
Nat Rev Cancer 6:663-73 (2006)
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)
KO pathway
 

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