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
acquired immunodeficiency syndromeVdr
acute kidney failureTp53
acute myeloid leukemiaMdm2 , Tp53
Addison's diseaseVdr
adenocarcinomaTp53 , Tp63
adenoid cystic carcinomaTp53
adenomaTp53
adrenal carcinomaTp53
Adrenal Gland NeoplasmsTp53
adrenocortical carcinomaTp53
ADULT syndromeTp63
adult T-cell leukemiaTp53 , Tp73
alopeciaVdr
alveolar rhabdomyosarcomaTp73
Alzheimer's diseaseMdm4 , Mre11a , Pin1 , Tp53
amyotrophic lateral sclerosisTp53
Anaplastic Thyroid CarcinomaTp53
angiosarcomaTp53
Animal Disease ModelsMre11a , Tp53
ankyloblepharon-ectodermal defects-cleft lip/palate syndromeTp63
aortic valve stenosisVdr
Arsenic PoisoningTp53
asthmaPin1 , Vdr
astrocytomaMre11a , Tp53
Ataxia Telangiectasia Like DisorderMre11a
Ataxia-Telangiectasia-Like Disorder 1Mre11a
atopic dermatitisVdr
autism spectrum disorderVdr
autoimmune hepatitisVdr
Autosomal Recessive Dyskeratosis CongenitaTp53
autosomal recessive limb-girdle muscular dystrophy type 2BVdr
Balkan nephropathyTp53
Barrett's esophagusVdr
basal cell carcinomaTp53 , Vdr
Behcet's diseaseVdr
biliary tract neoplasmMdm2
bladder exstrophyTp63
bladder exstrophy-epispadias-cloacal exstrophy complexTp63
bladder urothelial carcinomaTp53
bone development diseaseTp53
Bone Marrow NeoplasmsTp53
Brain InjuriesMdm2
brain ischemiaTp53
Brain NeoplasmsTp53
breast adenocarcinomaTp53
breast cancerTp53
Breast Cancer, FamilialTp53
breast diseaseTp63
Breast NeoplasmsMdm2 , Mdm4 , Mre11a , Pin1 , Tp53 , Tp63 , Tp73 , Vdr
bronchiolo-alveolar adenocarcinomaTp53
Bronchopulmonary DysplasiaVdr
carcinomaTp53 , Tp63
CardiomegalyPin1
cardiomyopathyTp53
carotid artery diseaseSrebf2 , Tp53
cataractTp53
Cecal NeoplasmsTp53
celiac diseaseEts1
Cell Transformation, NeoplasticMdm2 , Tp53 , Tp63
Central Nervous System NeoplasmsTp53
cerebral infarctionVdr
cervical cancerTp53
cervix carcinomaTp53
cervix uteri carcinoma in situTp63 , Tp73
CHARGE syndromeTp53
Chemotherapy-Induced Febrile NeutropeniaMdm2 , Tp53
cholangiocarcinomaMdm2 , Tp53
cholelithiasisSrebf2
cholesteatoma of middle earTp53
choroid plexus carcinomaTp53
choroid plexus papillomaTp53
Chromosome 17 DeletionTp53
chronic lymphocytic leukemiaTp53
Chronic Lymphocytic Leukemia, B-CellTp53 , Vdr
chronic obstructive pulmonary diseaseTp53
clear cell adenocarcinomaTp53
cleft lipTp63
cleft palateTp63
colon cancerTp53
colon carcinomaTp53
Colonic NeoplasmsMre11a , Tp53
colorectal adenocarcinomaTp53
colorectal cancerTp53
Colorectal NeoplasmsTp53 , Tp63
Combined Oxidative Phosphorylation Deficiency 11Tp53
common variable immunodeficiencySrebf2
Congenital Foot DeformitiesTp63
Congenital Hand DeformitiesTp63
Congenital Limb DeformitiesTp63
congestive heart failureTp53
Corneal InjuriesTp63
coronary artery diseaseVdr
coronary restenosisTp53
Craniofacial AbnormalitiesTp53 , Tp63
Crohn's diseaseVdr
Cutaneous Malignant Melanoma, Susceptibility To, 1Tp53
cutaneous T cell lymphomaTp53
dementiaMre11a
demyelinating diseaseTp53
diabetes mellitusVdr
Diabetic NephropathiesSrebf2 , Tp53
diabetic retinopathyVdr
Diamond-Blackfan anemiaTp53
diffuse large B-cell lymphomaTp53
dilated cardiomyopathyMdm4
disease of cellular proliferationMdm2 , Tp53 , Vdr
disease of metabolismSrebf2
Disease ProgressionSrebf2
Drug-induced NeutropeniaMdm2 , Tp53
Drug-Related Side Effects and Adverse ReactionsTp53
ductal carcinoma in situTp53
DwarfismVdr
dyskeratosis congenitaTp53
dystoniaMre11a
Ectodermal DysplasiaTp63
ectrodactyly, ectodermal dysplasia, and cleft lip-palate syndrome 3Tp63
EEC syndromeTp63
EmphysemaTp53
end stage renal failureSrebf2
endometrial cancerTp53
Endometrial NeoplasmsMre11a , Tp53 , Tp73
Erythema NodosumVdr
esophageal cancerTp53
esophageal carcinomaTp53
Esophageal NeoplasmsTp53
esophagus adenocarcinomaTp53 , Vdr
esophagus squamous cell carcinomaTp53
Experimental Autoimmune EncephalomyelitisVdr
Experimental Diabetes MellitusEts1 , Mdm2 , Tp53 , Tp63
Experimental NeoplasmsTp53 , Tp63
Fabry diseaseVdr
Female InfertilityTp53
Female Urogenital DiseasesTp63
Fetal Growth RetardationMdm2 , Vdr
Gallbladder NeoplasmsTp53
gastric adenocarcinomaTp53
gastroesophageal reflux diseaseTp63
Gaucher's diseaseTp53
genetic diseaseTp63 , Vdr
glioblastoma multiformeMdm4 , Tp53
Glomus Jugulare TumorSrebf2
grade III astrocytomaTp53
Graft vs Host DiseaseTp53
Graves' diseaseTp53 , Vdr
Head and Neck NeoplasmsTp53
head and neck squamous cell carcinomaTp53
hepatoblastomaTp53
hepatocellular carcinomaMdm2 , Srebf2 , Tp53
Hereditary Adrenocortical CarcinomaTp53
hereditary breast ovarian cancer syndromeMre11a , Tp53
Hereditary Neoplastic SyndromesMre11a , Tp53
hereditary spastic paraplegia 11Tp53
Hereditary Vitamin D-Resistant RicketsVdr
human immunodeficiency virus infectious diseaseMdm2 , Vdr
HypercalciuriaVdr
HypercholesterolemiaSrebf2
hypertensionPin1 , Tp53 , Vdr
hypertrophic cardiomyopathyTp53
HypothermiaMdm2
ichthyosisMdm2
InflammationTp73 , Vdr
Insulin ResistanceSrebf2
intermittent claudicationMdm2
Intervertebral Disc DisplacementVdr
Intimal HyperplasiaMdm2
ischemiaTp53
Kaposi's sarcomaTp53
keratosisTp53
kidney diseaseSrebf2
Lead PoisoningVdr
Leber hereditary optic neuropathyTp53
leishmaniasisVdr
lepromatous leprosyVdr
leukemiaTp53
Li-Fraumeni syndromeTp53
Li-Fraumeni Syndrome 2Tp53
Li-Fraumeni Syndrome 3Tp53
Li-Fraumeni-Like SyndromeTp53
Limb-Mammary SyndromeTp63
Lip NeoplasmsTp53
lipid storage diseaseSrebf2
Lipoyltransferase 1 DeficiencyTp53
liver cancerTp53
liver diseaseMdm2
liver neoplasmTp53
Liver Neoplasms, ExperimentalTp53
low tension glaucomaTp53
lung adenocarcinomaMre11a , Tp53 , Tp63
Lung NeoplasmsNfya , Tp53 , Tp63 , Tp73
lung small cell carcinomaTp53
lung squamous cell carcinomaTp53
Lymphatic MetastasisTp53
lymphomaTp53
Male Breast NeoplasmsVdr
male infertilityMdm2 , Tp53
malignant gliomaTp53
malignant mesotheliomaTp53
Mammary Neoplasms, ExperimentalPin1 , Tp53 , Vdr
marginal zone B-cell lymphomaTp53
medulloblastomaTp53
Megakaryoblastic Leukemia of Down SyndromeTp53
megakaryocytic leukemiaTp53
melanomaMdm2 , Tp53 , Vdr
mental depressionMre11a
MesotheliomaTp53
Mouth NeoplasmsEts1 , Tp53
Multiple AbnormalitiesTp63
multiple myelomaTp53
multiple sclerosisVdr
muscular dystrophyTp63
myelodysplastic syndromeMdm2 , Tp53
myelofibrosisTp53
myocardial infarctionTp53
Myocardial Reperfusion InjuryMdm2 , Tp53 , Vdr
myopiaVdr
Nasopharyngeal NeoplasmsTp53
nasopharynx carcinomaTp53
NeointimaPin1
Neoplasm MetastasisTp53 , Tp63 , Vdr
nephroblastomaTp53 , Tp73
nephrosisSrebf2
Nerve Sheath NeoplasmsTp53
nervous system diseaseTp53
Nervous System MalformationsTp73
neuroblastomaTp53 , Tp73
Neurocutaneous SyndromesMre11a
Neurologic ManifestationsTp73
non-Hodgkin lymphomaTp53
non-small cell lung carcinomaMdm2 , Tp53
Nose NeoplasmsTp53
obesitySrebf2 , Vdr
Odontogenic MyxomaTp53
Oral Lichen PlanusTp53
oral mucosa leukoplakiaTp53
oral submucous fibrosisTp53
Orofacial Cleft 8Tp63
Oropharyngeal NeoplasmsTp53
Osteoarthritis, KneeVdr
osteoporosisVdr
Osteoporosis, PostmenopausalVdr
osteosarcomaTp53
otitis mediaTp73
otosclerosisVdr
ovarian cancerMre11a , Tp53
Ovarian NeoplasmsMre11a , Tp53 , Tp63 , Tp73
ovarian serous cystadenocarcinomaTp53
ovary epithelial cancerTp53
pancreatic adenocarcinomaTp53
pancreatic cancerTp53 , Tp63
pancreatic carcinomaTp53
pancreatic ductal carcinomaMdm2
pancreatitisMdm2
paranasal sinus neoplasmTp53
Parasitic Liver DiseasesTp53
Parathyroid NeoplasmsVdr
Parkinson's diseaseVdr
Parkinsonian DisordersMre11a
Pediatric Adrenocortical CarcinomaTp53
penile neoplasmTp53
peptic esophagitisVdr
periodontitisVdr
Phyllodes TumorTp53
plasmacytomaTp53
pneumoconiosisMdm4
pneumoniaVdr
polycystic ovary syndromeVdr
PolyploidyTp53
post-traumatic stress disorderMdm2
pre-malignant neoplasmMdm2 , Tp53
precursor B lymphoblastic lymphoma/leukemiaTp53
precursor lymphoblastic lymphoma/leukemiaTp53
Premature AgingMdm2 , Tp53
priapismMdm2
primary biliary cirrhosisVdr
primary hyperparathyroidismVdr
primary open angle glaucomaTp53
prostate adenocarcinomaTp53
prostate cancerTp53 , Tp63
prostate carcinoma in situTp63
prostatic hypertrophyTp73
Prostatic NeoplasmsMdm2 , Mre11a , Srebf2 , Tp53 , Tp63 , Tp73 , Vdr
psoriasisTp53 , Vdr
pterygiumTp53
pulmonary hypertensionTp53
pulmonary tuberculosisVdr
Rapp-Hodgkin syndromeTp63
renal carcinomaTp53
renal cell carcinomaTp53 , Tp73 , Vdr
Reperfusion InjuryEts1 , Tp53
rhabdomyosarcomaTp53
rheumatoid arthritisVdr
ricketsVdr
sarcomaMdm2 , Tp53
Sarcoma Family Syndrome of Li and FraumeniTp53
schizophreniaTp53
secondary hyperparathyroidismPin1 , Vdr
serous cystadenocarcinomaTp53
Sezary's diseaseTp53
sickle cell anemiaMdm2
Skin AbnormalitiesTp63
skin melanomaVdr
Skin NeoplasmsTp53
small cell carcinomaTp53
Spinal Cord InjuriesMdm2 , Tp53
Spinal FracturesVdr
split hand-foot malformationTp63
split hand-foot malformation 4Tp63
Sporadic Papillary Renal Cell CarcinomaTp53
squamous cell carcinomaTp53 , Tp63 , Vdr
squamous cell neoplasmTp63
Stomach NeoplasmsMre11a , Srebf2 , Tp53
SunburnVdr
sweat gland neoplasmTp63
systemic lupus erythematosusEts1
T-Cell LymphomaTp53
temporal lobe epilepsyVdr
thymomaTp53
Thymus NeoplasmsTp53
Thyroid NeoplasmsTp53
Tongue NeoplasmsTp53
tongue squamous cell carcinomaTp53
transient cerebral ischemiaMdm2
transitional cell carcinomaTp53 , Tp63 , Tp73 , Vdr
Transplant RejectionPin1
Trigeminal Nerve InjuriesTp53
Triple Negative Breast NeoplasmsMre11a
tuberculoid leprosyVdr
tuberculosisVdr
Tumor Predisposition SyndromeMre11a , Tp53
Turner syndromeVdr
type 1 diabetes mellitusEts1 , Srebf2 , Vdr
type 2 diabetes mellitusEts1 , Srebf2 , Vdr
uremiaVdr
urinary bladder cancerMdm2 , Mre11a , Tp53 , Tp63 , Tp73
Urinary CalculiVdr
Urogenital NeoplasmsTp53
Urologic NeoplasmsTp53 , Tp63
uterine carcinosarcomaTp53
Uterine Cervical NeoplasmsTp53 , Tp73
Uterine NeoplasmsTp53
vascular dementiaSrebf2 , Tp53
Viral BronchiolitisVdr
visual epilepsySrebf2
Vitamin D DeficiencyVdr
vitiligoVdr
Vulvar Lichen SclerosusTp53
Vulvar NeoplasmsTp53 , Tp73
X-linked hypophosphatemic ricketsVdr
xeroderma pigmentosumTp53
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 pathwayTp53
antigen processing and presentation pathwayNfya , Nfyb , Nfyc
apoptotic cell death pathwayTp53
ataxia telangiectasia-mutated (ATM) signaling pathwayMre11a
basal cell carcinoma pathwayTp53
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 pathwayTp53
homologous recombination pathway of double-strand break repairMre11a
Huntington's disease pathwayTp53
hypoxia inducible factor pathwayEts1
interleukin-4 signaling pathwayEts1
measles pathwayTp53 , Tp73
melanoma pathwayMdm2 , Tp53
mitogen activated protein kinase signaling pathwayTp53
neurotrophic factor signaling pathwayTp53 , Tp73
non-homologous end joining pathway of double-strand break repairMre11a
non-small cell lung carcinoma 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 carcinoma pathwayEts1
Retinoic acid-inducible gene (RIG) I-like receptor signaling pathwayPin1
small cell lung carcinoma pathwayTp53
sterol regulatory element-binding protein signaling pathwaySrebf2
thyroid cancer pathwayTp53
titanium dioxide nanoparticle response pathwayTp53
tuberculosis pathwayNfya , Nfyb , Nfyc , Vdr
ubiquitin/proteasome degradation pathwayMdm2
urinary bladder cancer pathwayMdm2 , Tp53
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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