KEGG   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
hsa04115

Drug
D00341  Hydroxyurea (USP)
D08887  Cenersen sodium (USAN)
D09604  Dinaciclib (USAN/INN)
D09888  Drozitumab (USAN/INN)
D11148  Berzosertib (USAN/INN)
D11206  Prexasertib (USAN/INN)
D11219  Idasanutlin (USAN/INN)
D11455  Lerociclib (USAN)
D11787  Ceralasertib (JAN/USAN/INN)
D12321  Camonsertib (USAN)
D12378  Navtemadlin (USAN/INN)
D12399  Sulanemadlin (USAN/INN)
D12417  Siremadlin (USAN/INN)
D12418  Siremadlin succinate (USAN)
D12458  Ozekibart (USAN)
D12621  Milademetan (USAN/INN)
D12622  Milademetan tosylate (USAN)
D12834  Atirmociclib (USAN)
D12842  Brigimadlin (JAN/USAN/INN)
D12882  Tuvusertib (USAN/INN)
D13010  Lartesertib (USAN/INN)
Organism
Homo sapiens (human) [GN:hsa]
Gene
1017  CDK2; cyclin dependent kinase 2 [KO:K02206] [EC:2.7.11.22]
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]
1026  CDKN1A; cyclin dependent kinase inhibitor 1A [KO:K06625]
1029  CDKN2A; cyclin dependent kinase inhibitor 2A [KO:K06621]
10572  SIVA1; SIVA1 apoptosis inducing factor [KO:K22744]
10848  PPP1R13L; protein phosphatase 1 regulatory subunit 13 like [KO:K27356]
10912  GADD45G; growth arrest and DNA damage inducible gamma [KO:K04402]
1111  CHEK1; checkpoint kinase 1 [KO:K02216] [EC:2.7.11.1]
11200  CHEK2; checkpoint kinase 2 [KO:K06641] [EC:2.7.11.1]
143686  SESN3; sestrin 3 [KO:K10141]
1643  DDB2; damage specific DNA binding protein 2 [KO:K10140]
1647  GADD45A; growth arrest and DNA damage inducible alpha [KO:K04402]
25898  RCHY1; ring finger and CHY zinc finger domain containing 1 [KO:K10144] [EC:2.3.2.27]
25946  ZNF385A; zinc finger protein 385A [KO:K26543]
27113  BBC3; BCL2 binding component 3 [KO:K10132]
27244  SESN1; sestrin 1 [KO:K10141]
2810  SFN; stratifin [KO:K06644]
317  APAF1; apoptotic peptidase activating factor 1 [KO:K02084]
3479  IGF1; insulin like growth factor 1 [KO:K05459]
3486  IGFBP3; insulin like growth factor binding protein 3 [KO:K10138]
355  FAS; Fas cell surface death receptor [KO:K04390]
3732  CD82; CD82 molecule [KO:K06509]
4193  MDM2; MDM2 proto-oncogene [KO:K06643] [EC:2.3.2.27]
4194  MDM4; MDM4 regulator of p53 [KO:K10127]
4616  GADD45B; growth arrest and DNA damage inducible beta [KO:K04402]
472  ATM; ATM serine/threonine kinase [KO:K04728] [EC:2.7.11.1]
50484  RRM2B; ribonucleotide reductase regulatory TP53 inducible subunit M2B [KO:K10808] [EC:1.17.4.1]
5054  SERPINE1; serpin family E member 1 [KO:K03982]
51246  SHISA5; shisa family member 5 [KO:K10135]
51512  GTSE1; G2 and S-phase expressed 1 [KO:K10129]
5268  SERPINB5; serpin family B member 5 [KO:K10139]
5366  PMAIP1; phorbol-12-myristate-13-acetate-induced protein 1 [KO:K10131]
54205  CYCS; cytochrome c, somatic [KO:K08738]
545  ATR; ATR serine/threonine kinase [KO:K06640] [EC:2.7.11.1]
55240  STEAP3; STEAP3 metalloreductase [KO:K10142] [EC:1.16.1.-]
55367  PIDD1; p53-induced death domain protein 1 [KO:K10130]
56475  RPRM; reprimo, TP53 dependent G2 arrest mediator homolog [KO:K10128]
5728  PTEN; phosphatase and tensin homolog [KO:K01110] [EC:3.1.3.16 3.1.3.48 3.1.3.67]
575  ADGRB1; adhesion G protein-coupled receptor B1 [KO:K04596]
581  BAX; BCL2 associated X, apoptosis regulator [KO:K02159]
595  CCND1; cyclin D1 [KO:K04503]
596  BCL2; BCL2 apoptosis regulator [KO:K02161]
598  BCL2L1; BCL2 like 1 [KO:K04570]
6241  RRM2; ribonucleotide reductase regulatory subunit M2 [KO:K10808] [EC:1.17.4.1]
637  BID; BH3 interacting domain death agonist [KO:K04726]
63970  TP53AIP1; tumor protein p53 regulated apoptosis inducing protein 1 [KO:K13773]
64065  PERP; p53 apoptosis effector related to PMP22 [KO:K10136]
64326  COP1; COP1 E3 ubiquitin ligase [KO:K10143] [EC:2.3.2.27]
64393  ZMAT3; zinc finger matrin-type 3 [KO:K10137]
6477  SIAH1; siah E3 ubiquitin protein ligase 1 [KO:K04506] [EC:2.3.2.27]
7057  THBS1; thrombospondin 1 [KO:K16857]
7157  TP53; tumor protein p53 [KO:K04451]
7161  TP73; tumor protein p73 [KO:K10148]
7249  TSC2; TSC complex subunit 2 [KO:K07207]
836  CASP3; caspase 3 [KO:K02187] [EC:3.4.22.56]
83667  SESN2; sestrin 2 [KO:K20394]
841  CASP8; caspase 8 [KO:K04398] [EC:3.4.22.61]
842  CASP9; caspase 9 [KO:K04399] [EC:3.4.22.62]
84883  AIFM2; apoptosis inducing factor mitochondria associated 2 [KO:K22745]
8493  PPM1D; protein phosphatase, Mg2+/Mn2+ dependent 1D [KO:K10147] [EC:3.1.3.16]
8795  TNFRSF10B; TNF receptor superfamily member 10b [KO:K04722]
8797  TNFRSF10A; TNF receptor superfamily member 10a [KO:K04722]
891  CCNB1; cyclin B1 [KO:K05868]
894  CCND2; cyclin D2 [KO:K10151]
896  CCND3; cyclin D3 [KO:K10152]
898  CCNE1; cyclin E1 [KO:K06626]
900  CCNG1; cyclin G1 [KO:K10145]
901  CCNG2; cyclin G2 [KO:K10146]
9133  CCNB2; cyclin B2 [KO:K21770]
9134  CCNE2; cyclin E2 [KO:K06626]
92344  GORAB; golgin, RAB6 interacting [KO:K19748]
9538  EI24; EI24 autophagy associated transmembrane protein [KO:K10134]
9540  TP53I3; tumor protein p53 inducible protein 3 [KO:K10133] [EC:1.-.-.-]
983  CDK1; cyclin dependent kinase 1 [KO:K02087] [EC:2.7.11.22 2.7.11.23]
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
hsa04110  Cell cycle
hsa04210  Apoptosis
hsa04218  Cellular senescence
KO pathway
ko04115   

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