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; 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 activity; transcription factor 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 glucose starvation; chromatin assembly; circadian behavior; determination of adult life span; 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 induction of apoptosis; 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; multicellular organismal 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; phosphoinositide-mediated signaling; positive regulation of apoptosis; positive regulation of histone deacetylation; positive regulation of neuron apoptosis; positive regulation of peptidyl-tyrosine phosphorylation; positive regulation of protein export from nucleus; positive regulation of protein oligomerization; positive regulation of transcription from RNA polymerase II promoter; positive regulation of transcription, DNA-dependent; 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 mitochondrial membrane permeability; regulation of transcription, DNA-dependent; response to antibiotic; response to DNA damage stimulus; response to gamma radiation; response to X-ray; viral reproduction