p53: 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.
Protein type: Activator; Motility/polarity/chemotaxis; DNA-binding; Transcription factor; Tumor suppressor; Nuclear receptor co-regulator
Cellular Component: transcription factor TFIID complex; PML body; protein complex; nuclear matrix; mitochondrion; endoplasmic reticulum; replication fork; cytosol; nucleoplasm; nuclear body; transcription factor complex; mitochondrial matrix; cytoplasm; nuclear chromatin; nucleolus; intracellular; chromatin; nucleus
Molecular Function: protein C-terminus binding; identical protein binding; protease binding; protein phosphatase 2A binding; p53 binding; protein N-terminus binding; receptor tyrosine kinase binding; protein phosphatase binding; transcription factor binding; protein kinase binding; histone acetyltransferase binding; protein binding; copper ion binding; histone deacetylase regulator activity; enzyme binding; DNA binding; protein heterodimerization activity; sequence-specific DNA binding; chaperone binding; ubiquitin protein ligase binding; double-stranded DNA binding; damaged DNA binding; chromatin binding; transcription factor activity; ATP binding
Biological Process: central nervous system development; regulation of cell cycle; positive regulation of apoptosis; positive regulation of transcription, DNA-dependent; positive regulation of leukocyte migration; multicellular organismal development; T cell differentiation in the thymus; gastrulation; determination of adult life span; DNA damage response, signal transduction by p53 class mediator resulting in cell cycle arrest; response to organic cyclic substance; response to caffeine; regulation of apoptosis; response to antibiotic; cellular response to glucose starvation; protein localization; negative regulation of neuroblast proliferation; transforming growth factor beta receptor signaling pathway; response to vitamin B3; regulation of neuron apoptosis; cerebellum development; protein complex assembly; negative regulation of mitotic cell cycle; cell cycle arrest; ER overload response; response to UV; response to X-ray; response to drug; release of cytochrome c from mitochondria; somitogenesis; cell aging; chromatin assembly; positive regulation of cell cycle; response to organic nitrogen; response to amino acid stimulus; circadian behavior; rRNA transcription; regulation of transcription from RNA polymerase II promoter; positive regulation of peptidyl-tyrosine phosphorylation; negative regulation of DNA replication; negative regulation of fibroblast proliferation; regulation of intracellular pH; embryonic organ development; positive regulation of transcription from RNA polymerase II promoter; response to oxidative stress; negative regulation of transcription, DNA-dependent; negative regulation of apoptosis; regulation of tissue remodeling; transcription from RNA polymerase II promoter; G1 DNA damage checkpoint; response to metal ion; wound healing; DNA damage response, signal transduction by p53 class mediator; negative regulation of smooth muscle cell proliferation; apoptosis; negative regulation of transcription from RNA polymerase II promoter; chromosome organization and biogenesis; response to salt stress; entrainment of circadian clock by photoperiod; positive regulation of protein oligomerization; embryonic development ending in birth or egg hatching; negative regulation of cell proliferation; DNA damage response, signal transduction by p53 class mediator resulting in transcription of p21 class mediator; positive regulation of histone deacetylation; regulation of transcription, DNA-dependent; regulation of catalytic activity; T cell proliferation during immune response; double-strand break repair; positive regulation of neuron apoptosis; response to gamma radiation; DNA damage response, signal transduction by p53 class mediator resulting in induction of apoptosis; protein tetramerization; aging; mitochondrial DNA repair; negative regulation of proteolysis; response to retinoic acid; response to inorganic substance; in utero embryonic development; B cell lineage commitment; multicellular organism growth; regulation of cell proliferation; response to UV-B; neuron apoptosis; T cell lineage commitment; response to hyperoxia; protein import into nucleus, translocation; nucleotide-excision repair; response to cytokine stimulus; Ras protein signal transduction; DNA strand renaturation; negative regulation of cell growth; negative regulation of transforming growth factor beta receptor signaling pathway; response to DNA damage stimulus
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