KEGG PATHWAY: ko04115

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

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

K27356

RelA-associated inhibitor

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

K26543

zinc finger protein 385A

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

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