ALTERED P53 SIGNALING PATHWAY (PW:0000720)

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Description

The p53 tumor suppression transcription factor, many times referred to as the 'guardian of the genome' or as the 'cellular gatekeeper', is at the hub of many signaling and regulatory networks. It represents a critical node of cellular homeostasis integrating many cues emerging from exogenous and endogenous stresses and in response promoting, as necessary, cell cycle arrest, apoptosis or senescence, among others. Tp53 is one of the most commonly mutated gene in cancer. Some mutations are nonsense

Pathway Diagram:

Elsevier Inc. Pin1 target genes NFY complex Vdr p53 regulators p53 methylation Mdm4 --+> genome instability Mdm2 --+> genome instability Mdm2 ---- Tp53 Mdm4 Mdm2 Srebf2 ---- Tp53 Tp53 --+> cell migration Pin1 ---- Tp53 Tp53 --+> cell invasion Tp53 Tp53 --+> genome instability Mre11a ---- Tp53 Tp53 ---| ataxia telangiectasia-mutated (ATM) signaling pathway ataxia telangiectasia-mutated (ATM) signaling pathway MRN complex endogenous stress ---> Tp53 exogenous stress ---> Tp53 Tp73 --+> tumor suppression Tp63 --+> tumor suppression tumor suppression Tp73 Tp63 Tp53 ---| Tp73 Tp53 ---| Tp63 Tp73 ---> target genes NFY complex ---- Tp53 Tp53 ---- Tp73 Tp53 ---- Tp63 Tp63 ---> target genes Ets1 Tp53 --+> chemoresistance Ets1 ---- Tp53 Tp53 ---- Vdr Tp53 --+> cell proliferation Mdm2 ---| Tp53 Mdm4 ---- Tp53 p53, Mdm2 acetylation ---> Tp53 p53 methylation ---> Tp53 NO p53, Mdm2 acetylation ---| Mdm2 p53, Mdm2 phosphorylation ---> Mdm2 p53, Mdm2 phosphorylation ---> Tp53 ataxia telangiectasia-mutated (ATM) signaling pathway ---> p53, Mdm2 phosphorylation endogenous stress Mdm4 ---| Tp53 p53 ubiquitination Mdm2 ---- Mdm4 p53, Mdm2 phosphorylation p53, Mdm2 acetylation Srebf2 Breast Neoplasms cell invasion cell migration genome instability genome instability ---> Neoplasms Tp53 --+> cell survival cell survival cell survival ---> Neoplasms cell proliferation chemoresistance chemoresistance ---> Neoplasms cell proliferation ---> Neoplasms Neoplasms Mre11a exogenous stress
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Genes in Pathway:

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altered p53 signaling pathway term browser
Symbol Object Name JBrowse Chr Start Stop Reference
G Ets1 ETS proto-oncogene 1, transcription factor JBrowse link 8 33,756,634 33,879,625 RGD:8663430
G Mdm2 MDM2 proto-oncogene JBrowse link 7 60,719,060 60,743,618 RGD:2316186
RGD:8663434
G Mdm4 MDM4, p53 regulator JBrowse link 13 49,786,776 49,828,780 RGD:8663434
G Mre11a MRE11 homolog A, double strand break repair nuclease JBrowse link 8 13,304,355 13,350,329 RGD:8663431
G Nfya nuclear transcription factor Y subunit alpha JBrowse link 9 14,551,752 14,577,002 RGD:8663431
RGD:8663430
G Nfyb nuclear transcription factor Y subunit beta JBrowse link 7 27,081,667 27,097,481 RGD:8663431
RGD:8663430
G Nfyc nuclear transcription factor Y subunit gamma JBrowse link 5 139,687,442 139,760,154 RGD:8663431
RGD:8663430
G Pin1 peptidylprolyl cis/trans isomerase, NIMA-interacting 1 JBrowse link 8 21,669,236 21,680,615 RGD:8663430
G Srebf2 sterol regulatory element binding transcription factor 2 JBrowse link 7 123,381,082 123,438,605 RGD:8663431
RGD:8663430
G Tp53 tumor protein p53 JBrowse link 10 56,186,299 56,198,449 RGD:2316186
RGD:8693397
RGD:8663430
RGD:8663431
RGD:5490966
RGD:5133242
RGD:4143515
G Tp63 tumor protein p63 JBrowse link 11 78,234,853 78,456,559 RGD:8663431
RGD:8663430
G Tp73 tumor protein p73 JBrowse link 5 171,355,876 171,415,354 RGD:8663431
RGD:8663430
G Vdr vitamin D receptor JBrowse link 7 139,344,452 139,394,138 RGD:8663430

Pathway Gene Annotations

Disease Annotations Associated with Genes in the altered p53 signaling pathway
Disease TermsGene Symbols
Colitis, UlcerativeTp53
Pathway Annotations Associated with Genes in the altered p53 signaling pathway
Pathway TermsGene Symbols
aldosterone signaling pathwayNfyc
altered p53 signaling pathwayEts1 , Mdm2 , Mdm4 , Mre11a , Nfya , Nfyb , Nfyc , Pin1 , Srebf2 , Tp53 , Tp63 , Tp73 , Vdr
amyotrophic lateral sclerosis disease pathwayTp53
antigen processing and presentation pathwayNfya , Nfyb , Nfyc
apoptotic cell death pathwayTp53
ataxia telangiectasia-mutated (ATM) signaling pathwayMre11a
basal cell carcinoma pathwayTp53
bladder cancer pathwayMdm2 , Tp53
cell cycle pathway, mitoticMdm2 , Tp53
ceramide signaling pathwayTp53
chronic myeloid leukemia pathwayMdm2 , Tp53
colorectal cancer pathwayTp53
endocytosis pathwayMdm2
endometrial cancer pathwayTp53
glioma pathwayMdm2 , Tp53
hepatitis C virus infection pathwayTp53
homologous recombination pathway of double-strand break repairMre11a
Huntington disease pathwayTp53
hypoxia inducible factor pathwayEts1
interleukin-4 signaling pathwayEts1
measles infection pathwayTp53 , Tp73
melanoma pathwayMdm2 , Tp53
mitogen activated protein kinase signaling pathwayTp53
Mycobacterium tuberculosis infection pathwayNfya , Nfyb , Nfyc , Vdr
neurotrophic factor signaling pathwayTp53 , Tp73
non-homologous end joining pathway of double-strand break repairMre11a
non-small cell lung cancer pathwayTp53
p53 signaling pathwayMdm2 , Mdm4 , Pin1 , Tp53 , Tp73
p53-dependent G1/S DNA damage checkpoint pathwayTp53
pancreatic cancer pathwayTp53
platelet-derived growth factor signaling pathwayPin1
prostate cancer pathwayMdm2 , Tp53
Ras mediated signaling pathwayTp73
renal cell cancer pathwayEts1
Retinoic acid-inducible gene (RIG) I-like receptor signaling pathwayPin1
small cell lung cancer pathwayTp53
sterol regulatory element-binding protein signaling pathwaySrebf2
thyroid cancer pathwayTp53
titanium dioxide nanoparticle response pathwayTp53
ubiquitin/proteasome degradation pathwayMdm2
vinblastine pharmacodynamics pathwayTp53
vincristine pharmacodynamics pathwayTp53
vindesine pharmacodynamics pathwayTp53
vinorelbine pharmacodynamics pathwayTp53
Wnt signaling pathwayTp53
Phenotype Annotations Associated with Genes in the altered p53 signaling pathway
Phenotype TermsGene Symbols
increased tumor incidenceTp53

References Associated with the altered p53 signaling pathway:

Ontology Path Diagram:

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