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Symbol TP53 contributors: mct/ - updated : 22-11-2020
HGNC name tumor protein p53
HGNC id 11998
Corresponding disease
DEL17P131 chromosome 17p13.1 microdeletion
DKC8 dyskeratosis congenita 8
LFS1 Li-Fraumeni syndrome 1
Location 17p13.1      Physical location : 7.571.719 - 7.590.863
Synonym name
  • p53 tumor suppressor
  • tumor protein p53 (Li-Fraumeni syndrome)
  • p53 antigen
  • transformation-related protein 53
  • Synonym symbol(s) LFS1, TRP53, p53, FLJ92943
    TYPE functioning gene
    STRUCTURE 19.14 kb     12 Exon(s)
    10 Kb 5' upstream gene genomic sequence study
    MAPPING cloned Y linked N status confirmed
    Map pter - ABR ,D17S34 - D17S5 ,D17S525 - PFN1 - D17S873 - D17S866 - D17S539 - D17S878 - D17S559 - D17S570 ,D17S877 - TP53 - D17S561 ,D17S537 - cen
    TRANSCRIPTS type messenger
    identificationnb exonstypebpproduct
    ProteinkDaAAspecific expressionYearPubmed
    11 - 2586 43.7 393 - 2011 21402876
    11 - 2583 - 393 - 2011 21402876
    also called variant 2/isoform a
    12 - 2719 - 341 - 2011 21402876
    also called variant 3/isoform b or p53beta
    12 - 2646 - 346 - 2011 21402876
    also called variant 4/isoform c or p53gamma
    7 - 2271 - 261 - 2011 21402876
    also called variant 5/isoform d or delta133p53
    8 - 2331 - 214 - 2011 21402876
    also called variant 7/isoform f or delta133p53gamma
    8 - 2404 - 209 - 2011 21402876
    also called variant 6/isoform e or delta133p53beta
       expressed in (based on citations)
    cell lineage
    cell lines
  • proliferative cells, normal a transformed
  • rarely detected in normal cells
  • fluid/secretion
    at STAGE
    cell cycle     cell cycle, checkpoint
    life cycle G0 ,division
  • N-terminal transactivation domain (TAD) consists of two subdomains (TAD1 and TAD2), both of which exhibit independent transactivation functions and associate with a variety of proteins regulating transcription (TAD2 interacts with several DNA-binding domains such as RPA, positive cofactor 4 (PC4)
  • a loop-sheet-helix motif
  • a C terminal tetramerization domain, that regulates gene expression via multiple mechanisms depending on the tissue and target, and this leads to specific phenotypic effects
  • mono polymer homomer , dimer , tetramer
    interspecies homolog to rattus Tp53 (78,35 pc)
  • p53 family
  • CATEGORY DNA associated , transcription factor
    SUBCELLULAR LOCALIZATION     plasma membrane
  • TP53 co-localized with CLTC at the plasma membrane in response to EGF stimulation
  • export of TP53 from the nucleolus to the cytoplasm, resulting in the degradation of TP53 by ubiquitination
  • basic FUNCTION
  • required for G1 growth arrest by WAF1 (CDKN1A) following DNA damage or induction of apoptosis
  • regulating by its C terminus a G2 checkpoint through cyclin B1
  • transcriptional activator through acetylation of transactivation site by CREBBP
  • binding MDM2 resulting in transcriptional silencing and ubiquitin/proteasome dependent degradation of p53
  • putative teratologic suppressor gene and modulator of TFIIH (GTF2H), associated in nucleotide excision repair
  • activator of target genes promoting growth arrest or cell death in response to DNA damage
  • inducing CGR11, CGR19
  • playing a transcriptional role only in irradiated S phase cells (delta p53)
  • attenuating S phase progession via downregulation of cyclin A-cdk activity (delta p53)
  • maintaining the ATR-intra-S phase checkpoint to promote coordination repair and replication (delta p53)
  • negatively regulates tumor vessel formation and cell growth via the SEMA3F-NRP2 pathway
  • STK11, TP53, TUSC3 might play a role in the development of metastasis in larynx and pharynx squamous cell carcinomas
  • cytotoxic bomb that can be triggered by granzyme K, leading to potentiating killing efficacy)
  • contributes to transcription or replication regulatory mechanisms of mitochondria and also boosts mitochondrial genomic stability via stimulation of base excision repair
  • key role of TP53-dependent apoptosis in depleting adult stem cells after the accumulation of DNA damage, which leads to a decrease in tissue regeneration
  • has a pivotal role in the suppression of NOTCH-associated tumorigenesis in the mammary gland
  • stress-responsive tumor suppressor and potent growth inhibitor
  • cooperative and interdependent roles for ARID3A and TP53 in the transcriptional activation of CDKN1A in response to DNA damage
  • has a crucial role in governing cellular mechanisms in response to a broad range of genotoxic stresses
  • transcription factor that mediates tumor suppressor responses
  • TP53 expressed in T cells functions as a suppressor for autoimmunity by inducing Treg differentiation
  • MDM4/MDM2-TP53-IGF1 axis controls axonal regeneration, sprouting and functional recovery after CNS injury
  • TP53 has been demonstrated to promote ferroptosis via a transcription-dependent mechanism
  • TP53 and PPID in the mitochondria are critical for the Quercetin (QC)-mediated induction of cell death in hESCs
  • CELLULAR PROCESS cell cycle, checkpoint
    cell life, cell death/apoptosis
    nucleotide, repair
    nucleotide, transcription
  • unique MYB-DHRS2-MDM2-TP53 mitochondria-to-nucleus signaling pathway that may have functional significance for ER-positive breast cancers
  • TP53-SLC2A9 pathway is a novel antioxidant mechanism that uses uric acid to maintain ROS homeostasis and prevent accumulation of ROS-associated damage that potentially contributes to cancer development
  • a component
  • forming homodimer and homotetramer (delta p53)
  • AXIN1, PML and TP53 form a ternary complex
  • CDKN2A-MDM2-TP53 and the RPL11-MDM2-TP53 pathways are likely functionally connected
    DNA binding to a noncanonical p53-binding sequence in the CD44 promoter
    small molecule
  • modulator of TFIIH (GTF2H)
  • MDM2 binding
  • PIN1 (interaction dependent on the phosphorylation induced by DNA damage)
  • interacting with TP53INP1
  • interacting with MAML1
  • interacting with SMARCD1 via its tetramerization domain
  • interacting with ZBTB2
  • physical association between TP53 and BRCA2 may also have important implications in the control of homologous recombination
  • stabilized in a dose-dependent manner correlating with the level of TP53 target gene expression, by DHRS2 binding to MDM2
  • MDM2 binds directly to TP53 to inhibit transcription and export TP53 from the nucleolus to the cytoplasm, resulting in the degradation of TP53 by ubiquitination
  • MDM2-TP53 interaction is decreased upon deletion, mutation or acetylation of the TP53 C terminus
  • PBK interacts with the DBD domain of tumor suppressor TP53 and modulates expression of transcriptional targets including CDKN1A
  • interaction with TP63 (possible functional roles of TP63 in TP53-deficient cancer cells)
  • antagonistic relationship between NOTCH4 and TP53, which is controlled by the MDM2-dependent ubiquitylation and degradation of the NOTCH receptor
  • SENP3 interacts with TP53 and MDM2, desumoylates both proteins and bound to the acidic domain of MDM2, which also mediates the TP53 interaction, and competed with TP53 for binding
  • TP53 regulates autophagy through a direct molecular interaction with RB1CC1, a protein that is essential for the very apical step of autophagy initiation
  • novel regulator of TP53, modulating low level of MDM2-mediated TP53 ubiquitination in unstressed cells
  • role of ATF3 as an essential co-transcription factor for TP53 upon DNA damage
  • binds to the TP53 RE in PARK2 intron 1 and increases PARK2 transcription in cells
  • novel function for poly(ADP-ribose)ylation of TP53 in the gene-specific regulation of the transcriptional mode of TP53 on the promoter of MTA1
  • RECQL4 physically interacts with TP53 only in the absence of DNA damage (TP53-RECQL4 binding leads to the masking of the nuclear localization signal of TP53)
  • increased TP53 levels upon UBR5 depletion cause a G(1) arrest, as co-depletion of UBR5 and TP53 completely rescues this effect on cell cycle progression
  • RPL26 and NCL interact with each other and with a double-stranded RNA structure in TP53 mRNA to regulate TP53 translation after stress
  • E2F1 has an inhibitory role in TP53-mediated apoptosis
  • NDN required for neuronal development and survival, interacts with both SIRT1 and TP53 to facilitate TP53 deacetylation
  • TP53 is a target gene of ESR1 (feedback loop between ESR1 and TP53 and a biological role of TP53 in the DNA damage response in ER-positive breast cancers)
  • TP53-dependent transcriptional up-regulation of its target, E2F7, leads to repression of relevant gene expression
  • TP53 directly regulates MAF and PROX1, two important transcription factors controlling differentiation in the ocular lens
  • HEXIM1 interacts with two key TP53 regulators, nucleophosmin and double minute-2 protein (HDM2), implying a possible connection between HEXIM1 and the TP53 signaling pathway
  • functional interaction between CREBZF and the tumor suppressor TP53 (CREBZF may participate in the modulation of p53 tumor suppressor function)
  • TP63 but not TP53 is essential for DNA damage triggered transcriptional induction of BBC3 and PMAIP1 in primordial follicle oocytes
  • RUNX1 acts as a co-activator for TP53 in response to DNA damage
  • DNAJC7 is associated with TP53 in mammalian cells, and stabilizes TP53 by inhibiting complex formation between TP53 and MDM2
  • PRAP1 is a novel TP53 target gene
  • S100A4 modulates TP53 function in fibroblasts and thereby mediates myocardial interstitial fibrosis through two distinct mechanisms, cell proliferation and collagen expression
  • KAT6A is an acetylation regulator of TP53
  • TP53 rapidly induces VEGFA transcription upon hypoxia exposure by binding, in an HIF1A-dependent manner, to a highly conserved and functional TP53-binding site within the VEGFA promoter
  • TAF3 functions as an essential coactivator for TP53
  • important link between TP53 activation induced by DNA damage and MIRLET7A1 biogenesis
  • crosstalk between the TGFB1 and TP53 pathways defines a major node of regulation in the cellular stress response, enhancing drug resistance
  • folding of wild-type TP53 is promoted by an interaction with the chaperonin CCT complex
  • TP53-ZNF365 axis contributes to genomic stability in the setting of telomere dysfunction
  • SETD1A, SETD1B and EP300 act cooperatively, through direct interactions and coupled histone modifications, to facilitate the function of TP53
  • TXNIP is a new regulator of the ECD-MDM2-TP53 loop
  • legumain (LGMN) expression and its enzyme activity are regulated by TP53
  • RNF38 is an E3 ubiquitin ligase that may play a role in regulating TP53
  • TP53 represses expression of the rRNA methyl-transferase fibrillarin (FBL) by binding directly to FBL
  • CHCHD4 is necessary for the respiratory-dependent translocation of TP53 into the mitochondria
  • RBM24 is a target gene of the TP53 protein, and can regulate CDKN1A expression via mRNA stability
  • TOP3A binds to the TP53 and CDKN1A promoters and positively regulates their expression, contributing to the TP53-mediated tumor suppression
  • TP53&
  • 8209;PIAS3 interaction through the 1-52 amino acid region of TP53, reduces TP53&
    8209;MDM2 complex formation, which not only increases the half-life of TP53, but also its transactivation of target genes
  • JMJD6 antagonizes TP53 acetylation, promotes the association of TP53 with its negative regulator MDM4, and represses transcriptional activity of TP53
  • PELP1 interacts with TP53, functions as TP53-coactivator and is required for optimal activation of TP53 target genes under genomic stress
  • ISG15-dependent degradation of TP53 represents an alternative mechanism of controlling TP53 protein levels
  • TP73 was required for TP53 stabilization and accumulation under AMPK activation, but was dispensable under DNA damage
  • TRIM32 interacts with TP53 and promotes TP53 degradation through ubiquitination
  • XAF1 binds directly to the N-terminal proline-rich domain of TP53 and thus interferes with E3 ubiquitin ligase MDM2 binding and ubiquitination of TP53
  • TP53 interacted with C-terminal domain of YWHAG and induced YWHAG ubiquitination
  • suppression of TP53 by NOTCH3 is mediated by CCNG1 and sustained by MDM2 in hepatocellular carcinoma
  • HSP90B1 interacts with both TP53 and MDM2 to enhance MDM2-mediated TP53 ubiquitination and degradation
  • PATZ1, previously known for its transcriptional suppressor functions in T lymphocytes, is a crucial regulator of TP53
  • TP53 sequesters TAF9 from GLI1, which may contribute to inhibition of GLI1 activity by TP53 and potentially impact therapeutic success of agents targeting GLI-TAF9 interactions in cancer
  • KDM8 is a novel binding partner of TP53 and it functions as a positive modulator of cell cycle and cell proliferation mainly through the repression of TP53 pathway
  • PDCD5 interacts with the TP53 pathway to promote cell apoptosis
  • TGM2-mediated autophagy and CDKN1A-mediated cell cycle arrest are two important barriers in the TP53 pathway that prevent oncogenic transformation
  • SIVA1 interacts with tumor protein TP53 and with the member of the tumor necrosis factor receptor superfamily, stathmin, among others
  • DDB1 silencing activates TP53 pathway and leads to significant effects on cell cycle progression and rapid apoptosis
  • MYSM1 is a critical negative regulator of TP53 transcriptional programs in hematopoiesis, and its repression of BBC3/PUMA expression is essential for multipotent progenitor (MPP) survival, and partly contributes to maintaining HSC function
  • like CLCA2, MPZL2 is a type I transmembrane protein that is regulated by TP53 and TP63
  • CREBBP and EP300, activate transcription of TP53-regulated stress response genes and stabilize TP53 against ubiquitin-mediated degradation
  • TRIM65 inactivates TP53 through facilitating TP53 poly-ubiquitination and proteasome-mediated degradation
  • TP53, a key effector of the DNA damage response, negatively controls RBPJ gene transcription, through suppression of RBPJ promoter activity and, indirectly, by increased CDKN1A expression
  • CACUL1 is a novel regulator that negatively controls TP53 activity through the regulation of PML SUMOylation
  • TRIM71 interacts with TP53, controls its abundance by ubiquitination and antagonizes TP53-dependent pro-apoptotic and pro-differentiation response
  • TP53 played a role in iron homeostasis and was required for FDXR-mediated iron metabolism
  • direct molecular link between TP53 and DPP4 in the control of lipid metabolism
  • DDX3 regulates epigenetic transcriptional and translational activation of TP53 and colocalizes with TP53 at centrosome during mitosis to ensure proper mitotic progression and genome stability, which supports the tumor-suppressive role of DDX3X
  • NINJ1 is a target of TP53 and forms a feedback loop with TP53 by repressing TP53 mRNA translation
  • expression of USP5 and OTUD6A may be affected by TP53
  • TP53 can enhance ferroptosis by inhibiting the expression of SLC7A11 or by enhancing that of SAT1 and GLS2
  • TRIM65 binds to the N-terminus of TP53 tumor suppressor and thus competes with MDM2 for TP53 binding
  • down-regulation of TFAM increases the sensitivity of tumour cells to radiation via TP53/TIGAR signalling pathway
  • prolyl hydroxylase activity of EGLN3 is dispensable for its ability to stabilize TP53
  • LIMCH1 was a negative regulator implicated in the pathogenesis of lung cancer via modulating HUWE1 and TP53
  • function for NEK10 in the regulation of TP53 transcriptional activity through tyrosine phosphorylation
  • NEK10 has recently been shown to phosphorylate TP53 at Y327, promoting cell cycle arrest after exposure to DNA damaging agents
  • PRPF19 downregulation inhibits MDM4-mediated TP53 inactivation, resulting in induction of cellular senescence 7)
  • prominent RPA1-interacting partners are the tumor suppressor protein TP53, RAD51, ATRIP and ETAA1
  • cell & other
    activated by ATM in association with 14.3.3 proteins (YWHA*)
    conjugation to UBL1 (SUMO1)
    putative upregulated c-MYC target gene
    genotoxic stresses that can activate TP53, but also induce mutations in the TP53 gene, and thus select for TP53-mutated cells
    inhibited by its interaction with ZBTB2
    Phosphorylated by AURKB (Aurora B phosphorylates TP53 to accelerate the degradation of TP53 through the polyubiquitination-proteasome pathway, thus functionally suppressing the expression of TP53 target genes involved in cell cycle inhibition and apoptosis)
    Other both activated and repressed by lysine methylation
    deubiquitinated and stabilized by USP10
    corresponding disease(s) LFS1 , DEL17P131 , DKC8
    related resource p53 Mutation Database Analysis & Search
    IARC TP53 Mutation Database: Human somatic and germline TP53 mutations compiled from the literature
    p53 Mutation in Human Cancer
    Database of Germline p53 Mutations
    Other morbid association(s)
    TypeGene ModificationChromosome rearrangementProtein expressionProtein Function
    tumoral somatic mutation      
    in pancreas and endometrial carcinomas, in Barrett's adenocarcinoma (and esophageal squamous cell carcinoma), in hepatocellular carcinoma with poor prognosis and in Merckel cell carcinoma
    tumoral   LOH    
    in both APC and TP53 in colorectal tumors and TP53 only in hepatocellular carcinoma
    tumoral       loss of function
    in breast, adrenal, brain tumors
    tumoral somatic mutation      
    in basal cell carcinoma (BCC) of the skin
    tumoral       loss of function
    biallelic inactivation of derived from two distinct events, the germinative Arg337His mutation and the acquired loss of the entire chromosome 17, in adrenocortical tumor
    tumoral fusion      
    TP53/FXR2 fusion protein lacks the ability of wild-type TP53 to function as a transcription factor; TP53/FXR2 gene is the first reported TP53 fusion gene in acute megakaryoblastic leukemia cell
    tumoral       loss of function
    leading to depletion of mtDNA in breast cancer
    tumoral     --over  
    of KIT, TP53, and MKI67 reflects tumor grade and predicts survival in neuroendocrine carcinomas, but fail as prognostic markers in the subset of small cell lung cancer patients
    tumoral germinal mutation     loss of function
    in patients with primary ovarian, fallopian tube, or peritoneal cancers
  • to pancreatic cancer
  • to cancer
  • Variant & Polymorphism SNP
  • rs78378222 in the 3 prime untranslated region of TP53, that changes the AATAAA polyadenylation signal to AATACA associated to cutaneous basal cell carcinoma, prostate and colorectal adenoma
  • Candidate gene embryo implantation failure in human
    Therapy target
    PRIMA-1 (TP53-reactivation and induction of massive apoptosis) treatment could represent an interesting tool to reduce the level of mutant TP53 and kill cancer cells
    management of a therapeutic approach based on the reversal of epigenetic silencing of the crucial genes involved in regulatory pathways of the tumor suppressor TP53
  • essential role in regulating embryo implantation in mice through LIF transcription regulation
  • in Wdr74-deficient mouse embryos blocking Trp53 function rescues blastocyst formation and lineage differentiation