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; histone deacetylase regulator activity; identical protein binding; mRNA 3'-UTR binding; p53 binding; protease binding; protein binding; protein C-terminus 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; sequence-specific DNA binding; transcription factor activity; transcription factor binding; ubiquitin protein ligase binding
Biological Process: apoptosis; autophagy; B cell lineage commitment; cell aging; cell cycle arrest; cellular response to glucose starvation; cellular response to stress; central nervous system development; cerebellum development; chromatin assembly; chromosome organization and biogenesis; circadian behavior; circadian rhythm; 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; double-strand break repair; embryonic development ending in birth or egg hatching; embryonic organ development; entrainment of circadian clock by photoperiod; ER overload response; G1 DNA damage checkpoint; gastrulation; heart development; in utero embryonic development; mitochondrial DNA repair; multicellular organism growth; multicellular organismal development; negative regulation of apoptosis; negative regulation of cell growth; negative regulation of cell proliferation; negative regulation of DNA replication; negative regulation of fibroblast proliferation; negative regulation of mitotic cell cycle; negative regulation of neuroblast proliferation; negative regulation of proteolysis; negative regulation of smooth muscle cell proliferation; negative regulation of telomerase activity; negative regulation of transcription from RNA polymerase II promoter; negative regulation of transcription, DNA-dependent; negative regulation of transforming growth factor beta receptor signaling pathway; neuron apoptosis; nucleotide-excision repair; positive regulation of apoptosis; positive regulation of cell cycle; positive regulation of histone deacetylation; positive regulation of leukocyte migration; positive regulation of neuron apoptosis; positive regulation of peptidyl-tyrosine phosphorylation; positive regulation of protein oligomerization; positive regulation of transcription from RNA polymerase II promoter; positive regulation of transcription, DNA-dependent; protein complex assembly; protein homotetramerization; protein import into nucleus, translocation; protein localization; protein stabilization; regulation of apoptosis; regulation of cell cycle; regulation of cell proliferation; regulation of intracellular pH; regulation of neuron apoptosis; regulation of tissue remodeling; regulation of transcription from RNA polymerase II promoter; regulation of transcription, DNA-dependent; release of cytochrome c from mitochondria; response to DNA damage stimulus; response to drug; response to gamma radiation; response to oxidative stress; response to salt stress; response to UV; response to X-ray; rRNA transcription; somitogenesis; T cell differentiation in the thymus; T cell lineage commitment; T cell proliferation during immune response; transforming growth factor beta receptor signaling pathway; viral reproduction