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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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:8663430
RGD:8663431
G Nfyb nuclear transcription factor Y subunit beta JBrowse link 7 27,081,667 27,097,481 RGD:8663430
RGD:8663431
G Nfyc nuclear transcription factor Y subunit gamma JBrowse link 5 139,687,442 139,760,154 RGD:8663430
RGD:8663431
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:8663430
RGD:8663431
G Tp53 tumor protein p53 JBrowse link 10 56,186,299 56,198,449 RGD:2316186
RGD:4143515
RGD:5133242
RGD:5490966
RGD:8663430
RGD:8663431
RGD:8693397
G Tp63 tumor protein p63 JBrowse link 11 78,234,853 78,456,559 RGD:8663430
RGD:8663431
G Tp73 tumor protein p73 JBrowse link 5 171,355,876 171,415,354 RGD:8663430
RGD:8663431
G Vdr vitamin D (1,25- dihydroxyvitamin D3) 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
Abnormalities, MultipleTp63
Acquired Immunodeficiency SyndromeVdr
Acute Kidney InjuryTp53
Addison DiseaseVdr
AdenocarcinomaTp53 , Tp63
Adenocarcinoma of EsophagusTp53
Adenocarcinoma of LungTp53 , Tp63
Adenocarcinoma, Bronchiolo-AlveolarTp53
Adenocarcinoma, Clear CellTp53
AdenomaTp53
Adrenal Gland NeoplasmsTp53
Adrenocortical CarcinomaTp53
Adrenocortical Carcinoma, HereditaryTp53
Adrenocortical Carcinoma, PediatricTp53
Aging, PrematureMdm2 , Tp53
AlopeciaVdr
Alzheimer DiseaseMdm4 , Mre11a , Tp53
Amyotrophic Lateral SclerosisTp53
Anemia, Sickle CellMdm2
Aortic Valve StenosisVdr
Arsenic PoisoningTp53
Arthritis, RheumatoidVdr
AsthmaPin1 , Vdr
AstrocytomaMre11a , Tp53
Ataxia Telangiectasia Like DisorderMre11a
Ataxia-Telangiectasia-Like Disorder 1Mre11a
Balkan NephropathyTp53
Behcet SyndromeVdr
Biliary Tract NeoplasmsMdm2
Bladder Exstrophy and Epispadias ComplexTp63
Bone Diseases, DevelopmentalTp53
Bone Marrow NeoplasmsTp53
Brain InjuriesMdm2
Brain IschemiaTp53
Brain NeoplasmsTp53
Breast AdenocarcinomaTp53
Breast DiseasesTp63
Breast NeoplasmsMdm2 , Mdm4 , Mre11a , Pin1 , Tp53 , Tp63 , Tp73 , Vdr
Breast Neoplasms, MaleVdr
Bronchiolitis, ViralVdr
CarcinomaTp53 , Tp63
Carcinoma, Adenoid CysticTp53
Carcinoma, Basal CellTp53 , Vdr
Carcinoma, HepatocellularMdm2 , Srebf2 , Tp53
Carcinoma, Intraductal, NoninfiltratingTp53
Carcinoma, Non-Small-Cell LungMdm2 , Tp53
Carcinoma, Pancreatic DuctalMdm2
Carcinoma, Renal CellTp53 , Tp73 , Vdr
Carcinoma, Small CellTp53
Carcinoma, Squamous CellTp53 , Tp63 , Vdr
Carcinoma, Squamous Cell of Head and NeckTp53
Carcinoma, Transitional CellTp53 , Tp63 , Tp73 , Vdr
CardiomegalyPin1
CardiomyopathiesTp53
Cardiomyopathy, HypertrophicTp53
Carotid Artery DiseasesSrebf2 , Tp53
CataractTp53
Cecal NeoplasmsTp53
Celiac DiseaseEts1
Cell Transformation, NeoplasticMdm2 , Tp53 , Tp63
Central Nervous System NeoplasmsTp53
Cervical Intraepithelial NeoplasiaTp63 , Tp73
Chemotherapy-Induced Febrile NeutropeniaMdm2 , Tp53
CholangiocarcinomaMdm2 , Tp53
CholelithiasisSrebf2
Cholesteatoma, Middle EarTp53
Choroid Plexus CarcinomaTp53
Chromosome 17 DeletionTp53
Cleft LipTp63
Cleft PalateTp63
Colitis, UlcerativeTp53
Colonic NeoplasmsMre11a , Tp53
Colorectal NeoplasmsTp53 , Tp63
Corneal InjuriesTp63
Coronary Artery DiseaseVdr
Coronary RestenosisTp53
Craniofacial AbnormalitiesTp53 , Tp63
Crohn DiseaseVdr
Cystadenocarcinoma, SerousTp53
Dementia, VascularSrebf2 , Tp53
Demyelinating DiseasesTp53
Dermatitis, AtopicVdr
Diabetes MellitusVdr
Diabetes Mellitus, ExperimentalEts1 , Mdm2 , Tp53 , Tp63
Diabetes Mellitus, Type 1Ets1 , Srebf2 , Vdr
Diabetes Mellitus, Type 2Ets1 , Srebf2 , Vdr
Diabetic NephropathiesSrebf2 , Tp53
Diabetic RetinopathyVdr
Disease Models, AnimalTp53
Disease ProgressionSrebf2
Drug-induced NeutropeniaMdm2 , Tp53
Drug-Related Side Effects and Adverse ReactionsTp53
Dyskeratosis Congenita, Autosomal RecessiveTp53
Ectodermal DysplasiaTp63
EctrodactylyTp63
Ectrodactyly, Ectodermal Dysplasia, and Cleft Lip/Palate Syndrome 3Tp63
Ectrodactyly-Cleft Lip/Palate SyndromeTp63
EmphysemaTp53
Encephalomyelitis, Autoimmune, ExperimentalVdr
Endometrial NeoplasmsMre11a , Tp53 , Tp73
Epilepsy, Temporal LobeVdr
Esophageal NeoplasmsTp53
Esophageal Squamous Cell CarcinomaTp53
Familial Hypophosphatemic RicketsVdr
Female Urogenital DiseasesTp63
Fetal Growth RetardationMdm2
Foot Deformities, CongenitalTp63
Gallbladder NeoplasmsTp53
Genetic Diseases, InbornVdr
Glaucoma, Primary Open AngleTp53
GlioblastomaMdm4
GliomaTp53
Glomus Jugulare TumorSrebf2
Graft vs Host DiseaseTp53
Graves DiseaseTp53 , Vdr
Hand Deformities, CongenitalTp63
Hay-Wells SyndromeTp63
Heart FailureTp53
HemangiosarcomaTp53
Hepatitis, AutoimmuneVdr
HepatoblastomaTp53
Hereditary Breast and Ovarian Cancer SyndromeMre11a
Hereditary Vitamin D-Resistant RicketsVdr
HIV InfectionsMdm2 , Vdr
HypercalciuriaVdr
HypercholesterolemiaSrebf2
Hyperparathyroidism, SecondaryPin1 , Vdr
HypertensionPin1 , Tp53 , Vdr
Hypertension, PulmonaryTp53
HypothermiaMdm2
IchthyosisMdm2
Infertility, FemaleTp53
Infertility, MaleMdm2 , Tp53
InflammationVdr
Insulin ResistanceSrebf2
Intermittent ClaudicationMdm2
Intervertebral Disc DisplacementVdr
Intimal HyperplasiaMdm2
IschemiaTp53
Ischemic Attack, TransientMdm2
KeratosisTp53
Kidney DiseasesSrebf2
Kidney Failure, ChronicSrebf2
Lead PoisoningVdr
LeishmaniasisVdr
Leprosy, LepromatousVdr
Leprosy, TuberculoidVdr
LeukemiaTp53
Leukemia, Lymphocytic, Chronic, B-CellTp53 , Vdr
Leukemia, Megakaryoblastic, AcuteTp53
Leukemia, Megakaryoblastic, of Down SyndromeTp53
Leukemia, Myeloid, AcuteMdm2 , Tp53
Leukemia-Lymphoma, Adult T-CellTp53 , Tp73
Leukoplakia, OralTp53
Li-Fraumeni SyndromeTp53
Li-Fraumeni Syndrome 2Tp53
Li-Fraumeni-Like SyndromeTp53
Lichen Planus, OralTp53
Limb Deformities, CongenitalTp63
Limb-Mammary SyndromeTp63
Lip NeoplasmsTp53
LipidosesSrebf2
Liver Cirrhosis, BiliaryVdr
Liver DiseasesMdm2
Liver Diseases, ParasiticTp53
Liver NeoplasmsTp53
Liver Neoplasms, ExperimentalTp53
Low Tension GlaucomaTp53
Lung NeoplasmsNfya , Tp53 , Tp63 , Tp73
Lupus Erythematosus, SystemicEts1
Lymphatic MetastasisTp53
LymphomaTp53
Lymphoma, B-Cell, Marginal ZoneTp53
Lymphoma, Non-HodgkinTp53
Lymphoma, T-CellTp53
Lymphoma, T-Cell, CutaneousTp53
Mammary Neoplasms, ExperimentalPin1 , Tp53 , Vdr
MedulloblastomaTp53
MelanomaMdm2 , Tp53 , Vdr
Melanoma, Cutaneous MalignantVdr
Melanoma, Cutaneous Malignant, Susceptibility To, 1Tp53
MesotheliomaTp53
Mesothelioma, MalignantTp53
Metabolic DiseasesSrebf2
Mouth NeoplasmsEts1 , Tp53
Multiple MyelomaTp53
Multiple SclerosisVdr
Myelodysplastic SyndromesMdm2 , Tp53
Myocardial InfarctionTp53
Myocardial Reperfusion InjuryMdm2 , Tp53
MyopiaVdr
Nasopharyngeal carcinomaTp53
Nasopharyngeal NeoplasmsTp53
NeointimaPin1
Neoplasm MetastasisTp53 , Tp63 , Vdr
NeoplasmsMdm2 , Tp53 , Vdr
Neoplasms, ExperimentalTp53 , Tp63
Neoplasms, Squamous CellTp63
Neoplastic Syndromes, HereditaryMre11a , Tp53
NephrosisSrebf2
Nerve Sheath NeoplasmsTp53
Nervous System DiseasesTp53
Nervous System MalformationsTp73
NeuroblastomaTp53 , Tp73
Neurocutaneous SyndromesMre11a
Neurologic ManifestationsTp73
Nose NeoplasmsTp53
ObesitySrebf2 , Vdr
Odontogenic MyxomaTp53
Optic Atrophy, Hereditary, LeberTp53
Oral Submucous FibrosisTp53
Orofacial Cleft 8Tp63
Oropharyngeal NeoplasmsTp53
Osteoarthritis, KneeVdr
OsteoporosisVdr
Osteoporosis, PostmenopausalVdr
OsteosarcomaTp53
OtosclerosisVdr
Ovarian Epithelial CancerTp53
Ovarian NeoplasmsMre11a , Tp53 , Tp63 , Tp73
Pancreatic CarcinomaTp53
Pancreatic NeoplasmsTp53 , Tp63
PancreatitisMdm2
Papilloma, Choroid PlexusTp53
Paranasal Sinus NeoplasmsTp53
Penile NeoplasmsTp53
PeriodontitisVdr
Phyllodes TumorTp53
PneumoconiosisMdm4
PneumoniaVdr
PolyploidyTp53
Precancerous ConditionsMdm2 , Tp53
Precursor B-Cell Lymphoblastic Leukemia-LymphomaTp53
Precursor Cell Lymphoblastic Leukemia-LymphomaTp53
PriapismMdm2
Primary MyelofibrosisTp53
Propping Zerres SyndromeTp63
Prostatic HyperplasiaTp73
Prostatic Intraepithelial NeoplasiaTp63
Prostatic NeoplasmsMdm2 , Srebf2 , Tp53 , Tp63 , Tp73 , Vdr
PsoriasisTp53 , Vdr
PterygiumTp53
Pulmonary Disease, Chronic ObstructiveTp53
Rapp-Hodgkin SyndromeTp63
Reperfusion InjuryEts1 , Tp53
RhabdomyosarcomaTp53
Rhabdomyosarcoma, AlveolarTp73
RicketsVdr
SarcomaMdm2 , Tp53
Sarcoma Family Syndrome of Li and FraumeniTp53
Sarcoma, KaposiTp53
SchizophreniaTp53
SeizuresSrebf2
Sezary SyndromeTp53
Skin AbnormalitiesTp63
Skin NeoplasmsTp53
Small Cell Lung CarcinomaTp53
Spinal Cord InjuriesMdm2 , Tp53
Spinal FracturesVdr
Split-Hand/Foot Malformation 4Tp63
Squamous Cell Carcinoma of the TongueTp53
Stomach NeoplasmsMre11a , Srebf2 , Tp53
Stress Disorders, Post-TraumaticMdm2
SunburnVdr
Sweat Gland NeoplasmsTp63
ThymomaTp53
Thymus NeoplasmsTp53
Thyroid Carcinoma, AnaplasticTp53
Thyroid NeoplasmsTp53
Tongue NeoplasmsTp53
Transplant RejectionPin1
Trigeminal Nerve InjuriesTp53
Triple Negative Breast NeoplasmsMre11a
TuberculosisVdr
Tuberculosis, PulmonaryVdr
Tumor Predisposition SyndromeMre11a , Tp53
UremiaVdr
Urinary Bladder NeoplasmsMre11a , Tp53 , Tp63 , Tp73
Urinary CalculiVdr
Urogenital NeoplasmsTp53
Urologic NeoplasmsTp53 , Tp63
Uterine Cervical NeoplasmsTp53 , Tp73
Vitamin D DeficiencyVdr
VitiligoVdr
Vulvar Lichen SclerosusTp53
Vulvar NeoplasmsTp53 , Tp73
Wilms TumorTp73
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 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

References Associated with the altered p53 signaling pathway:

Ontology Path Diagram:

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