Cellular tumor antigen p53
Also known as: P53, TP53
Function
Multifunctional transcription factor that induces cell cycle arrest, DNA repair or apoptosis upon binding to its target DNA sequence. Acts as a tumor suppressor in many tumor types; induces growth arrest or apoptosis depending on the physiological circumstances and cell type. Negatively regulates cell division by controlling expression of a set of genes required for this process. One of the activated genes is an inhibitor of cyclin-dependent kinases. Apoptosis induction seems to be mediated either by stimulation of BAX and FAS antigen expression, or by repression of Bcl-2 expression. Its pro-apoptotic activity is activated via its interaction with PPP1R13B/ASPP1 or TP53BP2/ASPP2. However, this activity is inhibited when the interaction with PPP1R13B/ASPP1 or TP53BP2/ASPP2 is displaced by PPP1R13L/iASPP. In cooperation with mitochondrial PPIF is involved in activating oxidative stress-induced necrosis; the function is largely independent of transcription. Induces the transcription of long intergenic non-coding RNA p21 (lincRNA-p21) and lincRNA-Mkln1. LincRNA-p21 participates in TP53-dependent transcriptional repression leading to apoptosis and seems to have an effect on cell-cycle regulation. Implicated in Notch signaling cross-over. Prevents CDK7 kinase activity when associated to CAK complex in response to DNA damage, thus stopping cell cycle progression. Isoform 2 enhances the transactivation activity of isoform 1 from some but not all TP53-inducible promoters. Isoform 4 suppresses transactivation activity and impairs growth suppression mediated by isoform 1. Isoform 7 inhibits isoform 1-mediated apoptosis. Regulates the circadian clock by repressing CLOCK-BMAL1-mediated transcriptional activation of PER2.
Classification
- Family (Pfam)
- PF00870 P53, PF08563 P53_TAD, PF07710 P53_tetramer, PF18521 TAD2
- InterPro
- p53-like_TF_DNA-bd_sf, p53/RUNT-type_TF_DNA-bd_sf, P53_central_site, p53_DNA-bd, p53_TAD2, p53_tetramer_sf, p53_tetrameristn, p53_transactivation_domain, p53_tumour_suppressor
- Functional cluster
- Homeobox & Zinc-Finger Transcription Factors
Experimental structures · PDB · 295
- 1A1U NMR
- 1AIE X-ray 1.50A
- 1C26 X-ray 1.70A
- 1DT7 NMR
- 1GZH X-ray 2.60A
- 1H26 X-ray 2.24A
- 1HS5 NMR
- 1JSP NMR
- 1KZY X-ray 2.50A
- 1MA3 X-ray 2.00A
- 1OLG NMR
- 1OLH NMR
- … and 283 more
A predicted model is available from AlphaFold.
Gene Ontology · 115
- GO:0005813 centrosome
- GO:0000785 chromatin
- GO:0005737 cytoplasm
- GO:0005829 cytosol
- GO:0005783 endoplasmic reticulum
- GO:0005759 mitochondrial matrix
- GO:0005739 mitochondrion
- GO:0016363 nuclear matrix
- GO:0005730 nucleolus
- GO:0005654 nucleoplasm
- GO:0005634 nucleus
- GO:0016605 PML body
- GO:0032991 protein-containing complex
- GO:0005667 transcription regulator complex
- GO:0071889 14-3-3 protein binding
- GO:0036310 ATP-dependent DNA/DNA annealing activity
- GO:0003682 chromatin binding
- GO:0000987 cis-regulatory region sequence-specific DNA binding
- GO:0005507 copper ion binding
- GO:0001046 core promoter sequence-specific DNA binding
- GO:0097718 disordered domain specific binding
- GO:0003677 DNA binding
- GO:0001228 DNA-binding transcription activator activity, RNA polymerase II-specific
- GO:0003700 DNA-binding transcription factor activity
- GO:0000981 DNA-binding transcription factor activity, RNA polymerase II-specific
- GO:0001227 DNA-binding transcription repressor activity, RNA polymerase II-specific
- GO:0019899 enzyme binding
- GO:0140296 general transcription initiation factor binding
- GO:0042826 histone deacetylase binding
- GO:0042802 identical protein binding
- GO:0097371 MDM2/MDM4 family protein binding
- GO:0140693 molecular condensate scaffold activity
- GO:0140677 molecular function activator activity
- GO:0003730 mRNA 3'-UTR binding
- GO:0002039 p53 binding
- GO:1990841 promoter-specific chromatin binding
- GO:0002020 protease binding
- GO:0046982 protein heterodimerization activity
- GO:0051721 protein phosphatase 2A binding
- GO:0051087 protein-folding chaperone binding
- GO:0030971 receptor tyrosine kinase binding
- GO:0000978 RNA polymerase II cis-regulatory region sequence-specific DNA binding
- GO:0061629 RNA polymerase II-specific DNA-binding transcription factor binding
- GO:0001094 TFIID-class transcription factor complex binding
- GO:0000976 transcription cis-regulatory region binding
- GO:0001223 transcription coactivator binding
- GO:0031625 ubiquitin protein ligase binding
- GO:0008270 zinc ion binding
- GO:0006914 autophagy
- GO:0048539 bone marrow development
- GO:0072717 cellular response to actinomycin D
- GO:0071480 cellular response to gamma radiation
- GO:0042149 cellular response to glucose starvation
- GO:0071456 cellular response to hypoxia
- GO:0071479 cellular response to ionizing radiation
- GO:0034644 cellular response to UV
- GO:0071466 cellular response to xenobiotic stimulus
- GO:0090398 cellular senescence
- GO:0048512 circadian behavior
- GO:0008340 determination of adult lifespan
- GO:0006974 DNA damage response
- GO:0030330 DNA damage response, signal transduction by p53 class mediator
- GO:0043153 entrainment of circadian clock by photoperiod
- GO:0006983 ER overload response
- GO:0002244 hematopoietic progenitor cell differentiation
- GO:0060218 hematopoietic stem cell differentiation
- GO:0008104 intracellular protein localization
- GO:0097193 intrinsic apoptotic signaling pathway
- GO:0072332 intrinsic apoptotic signaling pathway by p53 class mediator
- GO:0042771 intrinsic apoptotic signaling pathway in response to DNA damage by p53 class mediator
- GO:0070059 intrinsic apoptotic signaling pathway in response to endoplasmic reticulum stress
- GO:0031571 mitotic G1 DNA damage checkpoint signaling
- GO:0009299 mRNA transcription
- GO:0043066 negative regulation of apoptotic process
- GO:0030308 negative regulation of cell growth
- GO:0008285 negative regulation of cell population proliferation
- GO:0045892 negative regulation of DNA-templated transcription
- GO:0048147 negative regulation of fibroblast proliferation
- GO:1903451 negative regulation of G1 to G0 transition
- GO:0051097 negative regulation of helicase activity
- GO:1905856 negative regulation of pentose-phosphate shunt
- GO:0032211 negative regulation of telomere maintenance via telomerase
- GO:0000122 negative regulation of transcription by RNA polymerase II
- GO:0006289 nucleotide-excision repair
- GO:0097252 oligodendrocyte apoptotic process
- GO:0090403 oxidative stress-induced premature senescence
- GO:0043065 positive regulation of apoptotic process
- GO:2000774 positive regulation of cellular senescence
- GO:0045893 positive regulation of DNA-templated transcription
- GO:1900119 positive regulation of execution phase of apoptosis
- GO:0010628 positive regulation of gene expression
- GO:2001244 positive regulation of intrinsic apoptotic signaling pathway
- GO:1902895 positive regulation of miRNA transcription
- GO:0062100 positive regulation of programmed necrotic cell death
- GO:2000379 positive regulation of reactive oxygen species metabolic process
- GO:0090200 positive regulation of release of cytochrome c from mitochondria
- GO:0045899 positive regulation of RNA polymerase II transcription preinitiation complex assembly
- GO:0070245 positive regulation of thymocyte apoptotic process
- GO:0045944 positive regulation of transcription by RNA polymerase II
- GO:0051262 protein tetramerization
- GO:0065003 protein-containing complex assembly
- GO:0007265 Ras protein signal transduction
- GO:0042981 regulation of apoptotic process
- GO:0051726 regulation of cell cycle
- GO:1902749 regulation of cell cycle G2/M phase transition
- GO:0006355 regulation of DNA-templated transcription
- GO:0006357 regulation of transcription by RNA polymerase II
- GO:0090399 replicative senescence
- GO:0046677 response to antibiotic
- GO:0010332 response to gamma radiation
- GO:0072331 signal transduction by p53 class mediator
- GO:0045815 transcription initiation-coupled chromatin remodeling
- GO:0033209 tumor necrosis factor-mediated signaling pathway
- GO:0060333 type II interferon-mediated signaling pathway
- GO:0016032 viral process
Disease associations
- esophageal cancer MONDO:0007576
- Li-Fraumeni syndrome MONDO:0018875
- OMIM:191170 RAW:OMIM_191170
- adrenocortical carcinoma, hereditary MONDO:0008734
- lung cancer MONDO:0008903
- choroid plexus papilloma MONDO:0009837
- head and neck squamous cell carcinoma MONDO:0010150
- basal cell carcinoma, susceptibility to, 7 MONDO:0013876
- bone marrow failure syndrome 5 MONDO:0032573
Drugs targeting this protein · 5
- IDASANUTLIN inhibitor
- NAVTEMADLIN inhibitor
- EPRENETAPOPT stabiliser
- SIREMADLIN inhibitor
- ALRIZOMADLIN inhibitor
Related proteins · sequence + function similarity
- Cellular tumor antigen p53 0.99
- Cellular tumor antigen p53 0.99
- Cellular tumor antigen p53 0.99
- Cellular tumor antigen p53 0.99
- Cellular tumor antigen p53 0.98
- Cellular tumor antigen p53 0.98
- Cellular tumor antigen p53 0.97
- Cellular tumor antigen p53 0.97
- Cellular tumor antigen p53 0.97
- Cellular tumor antigen p53 0.97
- Cellular tumor antigen p53 0.96
- Cellular tumor antigen p53 0.96
Co-cited proteins · studied together in the literature
- Cellular tumor antigen p53 12 shared papers
- Bromodomain-containing protein 7 2 shared papers
- F-box only protein 42 1 shared papers
- E3 ubiquitin-protein ligase Mdm2 12 shared papers
- Protein BANP 2 shared papers
- Armadillo repeat-containing protein 10 1 shared papers
- Zinc finger protein 385B 1 shared papers
- Zinc finger protein 768 1 shared papers
- WW domain-containing oxidoreductase 2 shared papers
- Histone-lysine N-methyltransferase SETD7 3 shared papers
- Protein S100-A4 2 shared papers
- Nucleolar complex protein 2 homolog 2 shared papers
Literature · 225 cited papers
- Alanyl-tRNA synthetase, AARS1, is a lactate sensor and lactyltransferase that lactylates p53 and contributes to tumorigenesis. Cell · 2024
- Phosphorylation and specific DNA improved the incorporation ability of p53 into functional condensates. Int. J. Biol. Macromol. · 2023
- Phase separation of p53 induced by its unstructured basic region and prevented by oncogenic mutations in tetramerization domain. Int. J. Biol. Macromol. · 2022
- Ser392 phosphorylation modulated a switch between p53 and transcriptional condensates. Biochim. Biophys. Acta · 2022
- Aldolase B suppresses hepatocellular carcinogenesis by inhibiting G6PD and pentose phosphate pathways. Nat. Cancer · 2020
- The ORF45 protein of Kaposi Sarcoma-associated Herpesvirus (KSHV) is an inhibitor of p53 signaling during viral reactivation. J. Virol. · 2021
- ZNF768 links oncogenic RAS to cellular senescence. Nat. Commun. · 2021
- DAZAP2 acts as specifier of the p53 response to DNA damage. Nucleic Acids Res. · 2021
- Structure Determination of the Transactivation Domain of p53 in Complex with S100A4Using Annexin A2 as a Crystallization Chaperone. Structure · 2020
- PMID 32144153 J. Biol. Chem. · 2020
- Liquid-like droplet formation by tumor suppressor p53 induced by multivalent electrostatic interactions between two disordered domains. Sci. Rep. · 2020
- VRK1 functional insufficiency due to alterations in protein stability or kinase activity of human VRK1 pathogenic variants implicated in neuromotor syndromes. Sci. Rep. · 2019
- … and 213 more in the literature graph