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FLASH GENE
Symbol TP53 contributors: mct/ - updated : 10-06-2011
HGNC name tumor protein p53
HGNC id 11998
Corresponding disease
DEL17P131 chromosome 17p13.1 microdeletion
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
    DNA
    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
    Physical map
    ZBTB4 17p13.2 zinc finger and BTB domain containing 4 POLR2A 17p13.1 polymerase (RNA) II (DNA directed) polypeptide A, 220kDa TNFSF12 17p13.1 tumor necrosis factor (ligand) superfamily, member 12 TNFSF13 17p13.1 tumor necrosis factor (ligand) superfamily, member 13 SENP3 17p13 tumor necrosis factor (ligand) superfamily, member 13 EIF4A1 17p13.1 eukaryotic translation initiation factor 4A, isoform 1 CD68 17p13.1 CD68 antigen MPDU1 17p13.1-p12 mannose-P-dolichol utilization defect 1 SOX15 17p12.3 SRY (sex determining region Y)-box 15 FXR2 17p13.1 fragile X mental retardation, autosomal homolog 2 SAT2 17p13.2 spermidine/spermine N1-acetyltransferase 2 SHBG 17p13.1 sex hormone-binding globulin ATP1B2 17p13.1 ATPase, Na+/K+ transporting, beta 2 polypeptide TP53 17p13.1 tumor protein p53 (Li-Fraumeni syndrome) FLJ10385 17p13.2 hypothetical protein FLJ10385 EFNB3 17p13.1-p11.2 ephrin-B3 LOC284158 17p13.2 similar to KIAA1503 protein
    RNA
    TRANSCRIPTS type messenger
    identificationnb exonstypebpproduct
    ProteinkDaAAspecific expressionYearPubmed
    11 - 2586 43.7 393 - -
    11 - 2583 - 393 - -
    also called variant 2/isoform a
    12 - 2719 - 341 - -
    also called variant 3/isoform b or p53beta
    12 - 2646 - 346 - -
    also called variant 4/isoform c or p53gamma
    7 - 2271 - 261 - -
    also called variant 5/isoform d or delta133p53
    8 - 2331 - 214 - -
    also called variant 7/isoform f or delta133p53gamma
    8 - 2404 - 209 - -
    also called variant 6/isoform e or delta133p53beta
    EXPRESSION
    Type
       expressed in (based on citations)
    organ(s)
    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
    PROTEIN
    PHYSICAL PROPERTIES
    STRUCTURE
    motifs/domains
  • 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
    • mono polymer homomer , dimer , tetramer
    HOMOLOGY
    interspecies homolog to rattus Tp53 (78,35 pc)
    Homologene
    FAMILY
  • p53 family
    • CATEGORY DNA associated , transcription factor
    SUBCELLULAR LOCALIZATION     intracellular
    intracellular,cytoplasm
    intracellular,nucleus,nucleolus
    text
  • 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
    • CELLULAR PROCESS cell cycle, checkpoint
    cell life, cell death/apoptosis
    nucleotide, repair
    nucleotide, transcription
    PHYSIOLOGICAL PROCESS
    PATHWAY
    metabolism
    signaling
    unique MYB-DHRS2-MDM2-TP53 mitochondria-to-nucleus signaling pathway that may have functional significance for ER-positive breast cancers
    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
    • INTERACTION
    DNA binding to a noncanonical p53-binding sequence in the CD44 promoter
    RNA
    small molecule
    protein
  • 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
  • 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
  • novel regulator of TP53, modulating low level of MDM2-mediated TP53 ubiquitination in unstressed cells
  • binds to the TP53 RE in PARK2 intron 1 and increases PARK2 transcription in cells
    • cell & other
    REGULATION
    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
    Other both activated and repressed by lysine methylation
    deubiquitinated and stabilized by USP10
    ASSOCIATED DISORDERS
    corresponding disease(s) LFS1 , DEL17P131
    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
    Susceptibility
  • 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
    Marker
    Therapy target
    SystemTypeDisorderPubmed
    cancer  
    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
    cancer  
    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
    ANIMAL & CELL MODELS
    essential role in regulating embryo implantation in mice through LIF transcription regulation