KEGG PATHWAY: hsa04115

PATHWAY: hsa04115

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

Pathway map

hsa04115

p53 signaling pathway

Disease

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)

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 binding protein homolog (mouse) [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 (TNF receptor superfamily, member 6) [KO:K04390]
55367	PIDD; p53-induced death domain protein [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 homolog 5 (Xenopus laevis) [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

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)

Reference

PMID:15838523

Authors

Harris SL, Levine AJ.

Title

The p53 pathway: positive and negative feedback loops.

Journal

Oncogene 24:2899-908 (2005)

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)

Reference

PMID:11313928

Authors

Taylor WR, Stark GR.

Title

Regulation of the G2/M transition by p53.

Journal

Oncogene 20:1803-15 (2001)

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)

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)

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)

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)

Reference

PMID:16915296

Authors

Sherr CJ.

Title

Divorcing ARF and p53: an unsettled case.

Journal

Nat Rev Cancer 6:663-73 (2006)

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)

KO pathway

ko04115

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Disease (8)   
   KEGG DISEASE (8)   
Drug (7)   
   KEGG DRUG (7)   
Genome (1)   
   KEGG GENOME (1)   
Gene (68)   
   KEGG GENES (68)   
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