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: Nuclear receptor co-regulator; Tumor suppressor; Activator; Motility/polarity/chemotaxis; Transcription factor; DNA-binding
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: identical protein binding; protease binding; protein phosphatase 2A binding; protein phosphatase binding; transcription factor binding; histone acetyltransferase binding; enzyme binding; sequence-specific DNA binding; double-stranded DNA binding; transcription factor activity; ATP binding; protein C-terminus binding; p53 binding; protein N-terminus binding; receptor tyrosine kinase binding; protein kinase binding; protein binding; histone deacetylase regulator activity; copper ion binding; DNA binding; protein heterodimerization activity; chaperone binding; ubiquitin protein ligase binding; damaged DNA binding; chromatin binding
Biological Process: central nervous system development; positive regulation of apoptosis; regulation of cell cycle; multicellular organismal development; positive regulation of leukocyte migration; positive regulation of transcription, DNA-dependent; T cell differentiation in the thymus; gastrulation; determination of adult life span; response to organic cyclic substance; DNA damage response, signal transduction by p53 class mediator resulting in cell cycle arrest; response to caffeine; response to antibiotic; regulation of apoptosis; 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 X-ray; response to UV; response to drug; somitogenesis; release of cytochrome c from mitochondria; cell aging; chromatin assembly; positive regulation of cell cycle; response to amino acid stimulus; response to organic nitrogen; circadian behavior; rRNA transcription; regulation of transcription from RNA polymerase II promoter; positive regulation of peptidyl-tyrosine phosphorylation; negative regulation of fibroblast proliferation; negative regulation of DNA replication; 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; G1 DNA damage checkpoint; transcription from RNA polymerase II promoter; response to metal ion; DNA damage response, signal transduction by p53 class mediator; wound healing; 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; T cell proliferation during immune response; regulation of catalytic activity; positive regulation of neuron apoptosis; double-strand break repair; response to gamma radiation; DNA damage response, signal transduction by p53 class mediator resulting in induction of apoptosis; protein tetramerization; aging; negative regulation of proteolysis; mitochondrial DNA repair; response to inorganic substance; response to retinoic acid; in utero embryonic development; multicellular organism growth; B cell lineage commitment; regulation of cell proliferation; response to UV-B; T cell lineage commitment; neuron apoptosis; response to hyperoxia; protein import into nucleus, translocation; nucleotide-excision repair; response to cytokine stimulus; DNA strand renaturation; Ras protein signal transduction; negative regulation of cell growth; negative regulation of transforming growth factor beta receptor signaling pathway; response to DNA damage stimulus
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