a transcription factor and major tumor suppressor that plays a major role in regulating cellular responses to DNA damage and other genomic aberrations. Activation of p53 can lead to either cell cycle arrest and DNA repair or apoptosis. More than 50 percent of human tumors contain a mutation or deletion of the TP53 gene. p53 is modified post-translationally at multiple sites. DNA damage induces phosphorylation of p53 at S15, S20 and S37, reducing its interaction with the oncoprotein MDM2. MDM2 inhibits p53 accumulation by targeting it for ubiquitination and proteasomal degradation. Phosphorylated by many kinases including Chk2 and Chk1 at S20, enhancing its tetramerization, stability and activity. The phosphorylation by CAK at S392 is increased in human tumors and has been reported to influence the growth suppressor function, DNA binding and transcriptional activation of p53. Phosphorylation of p53 at S46 regulates the ability of p53 to induce apoptosis. The acetylation of p53 appears to play a positive role in the accumulation of p53 during the stress response. Following DNA damage, p53 becomes acetylated at K382, enhancing its binding to DNA. Deacetylation of p53 can occur through interaction with SIRT1, a deacetylase that may be involved in cellular aging and the DNA damage response. p53 regulates the transcription of a set of genes encoding endosomal proteins that regulate endosomal functions. These include STEAP3 and CHMP4C, which enhance exosome production, and CAV1 and CHMP4C, which produce a more rapid endosomal clearance of the EGFR from the plasma membrane. DNA damage regulates a p53-mediated secretory pathway, increasing the secretion of some proteins such as Hsp90, SERPINE1, SERPINB5, NKEF-A, and CyPA, and inhibiting the secretion of others including CTSL and IGFBP-2. Two alternatively spliced human isoforms have been reported. Isoform 2 is expressed in quiescent lymphocytes. Seems to be non-functional. May be produced at very low levels due to a premature stop codon in the mRNA, leading to nonsense-mediated mRNA decay. Note: This description may include information from UniProtKB.
Molecular Function: ATP binding; chaperone binding; chromatin binding; copper ion binding; damaged DNA binding; DNA binding; DNA binding transcription factor activity; enzyme binding; histone acetyltransferase binding; histone deacetylase binding; identical protein binding; mRNA 3'-UTR binding; p53 binding; protease binding; protein binding; protein heterodimerization activity; protein kinase binding; protein N-terminus binding; protein phosphatase 2A binding; protein phosphatase binding; protein self-association; receptor tyrosine kinase binding; transcription factor binding; transcription regulatory region DNA binding; ubiquitin protein ligase binding; zinc ion binding
Biological Process: autophagy; base-excision repair; cell aging; cell cycle arrest; cell differentiation; cell proliferation; cellular response to DNA damage stimulus; cellular response to gamma radiation; cellular response to glucose starvation; cellular response to hypoxia; cellular response to ionizing radiation; cellular response to UV; chromatin assembly; circadian behavior; determination of adult lifespan; DNA damage response, signal transduction by p53 class mediator; DNA damage response, signal transduction by p53 class mediator resulting in cell cycle arrest; DNA damage response, signal transduction by p53 class mediator resulting in transcription of p21 class mediator; DNA strand renaturation; entrainment of circadian clock by photoperiod; ER overload response; G1 DNA damage checkpoint; intrinsic apoptotic signaling pathway by p53 class mediator; intrinsic apoptotic signaling pathway in response to DNA damage by p53 class mediator; mRNA transcription; multicellular organism development; negative regulation of apoptosis; negative regulation of cell growth; negative regulation of cell proliferation; negative regulation of fibroblast proliferation; negative regulation of helicase activity; negative regulation of telomerase activity; negative regulation of transcription from RNA polymerase II promoter; negative regulation of transcription, DNA-dependent; nucleotide-excision repair; oxidative stress-induced premature senescence; positive regulation of apoptosis; positive regulation of cell cycle arrest; positive regulation of execution phase of apoptosis; positive regulation of gene expression; positive regulation of histone deacetylation; positive regulation of intrinsic apoptotic signaling pathway; positive regulation of neuron apoptotic process; positive regulation of peptidyl-tyrosine phosphorylation; positive regulation of protein export from nucleus; positive regulation of protein insertion into mitochondrial membrane involved in apoptotic signaling pathway; positive regulation of protein oligomerization; positive regulation of reactive oxygen species metabolic process; positive regulation of release of cytochrome c from mitochondria; positive regulation of transcription from RNA polymerase II promoter; positive regulation of transcription from RNA polymerase II promoter in response to endoplasmic reticulum stress; positive regulation of transcription, DNA-templated; proteasomal ubiquitin-dependent protein catabolic process; protein complex assembly; protein deubiquitination; protein homotetramerization; protein localization; protein tetramerization; Ras protein signal transduction; regulation of apoptosis; regulation of cell cycle G2/M phase transition; regulation of mitochondrial membrane permeability; regulation of transcription, DNA-templated; replicative senescence; response to antibiotic; response to gamma radiation; response to X-ray; signal transduction by p53 class mediator; transcription from RNA polymerase II promoter; viral process