p53
a ubiquitous transcription factor and major tumor suppressor in many tumor types. 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. Involved in cell cycle regulation as a trans-activator that acts to negatively regulate cell division by controlling a set of genes required for this process. Apoptosis induction seems to be mediated either by stimulation of BAX and FAS antigen expression, or by repression of Bcl-2 expression. In cooperation with mitochondrial PPIF is involved in activating oxidative stress-induced necrosis; the function is largely independent of transcription. Induces the transcription of long intergenic non-coding RNA p21 (lincRNA-p21) and lincRNA-Mkln1. LincRNA-p21 participates in TP53-dependent transcriptional repression leading to apoptosis and seems to have an effect on cell-cycle regulation. Implicated in Notch signaling cross-over. Prevents CDK7 kinase activity when associated to CAK complex in response to DNA damage, thus stopping cell cycle progression. p53 is modified post-translationally at multiple sites. DNA damage induces phosphorylation at multiple sites, reducing its interaction with the oncoprotein MDM2. MDM2 inhibits p53 accumulation by targeting it for ubiquitination and proteasomal degradation. Phosphorylation by many kinases including Chk2 and Chk1 enhances its tetramerization, stability and activity. The phosphorylation by CAK increases in human tumors and has been reported to influence the growth suppressor function, DNA binding and transcriptional activation of p53.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. Nine human isoforms generated by alternative promoter usage or alternative splicing have been reported. Isoform 2 enhances the transactivation activity of isoform 1 from some but not all TP53-inducible promoters. Isoform 4 suppresses transactivation activity and impairs growth suppression mediated by isoform 1. Isoform 7 inhibits isoform 1-mediated apoptosis. Isoforms are expressed in a wide range of normal tissues but in a tissue-dependent manner. Isoform 2 is expressed in most normal tissues but is not detected in brain, lung, prostate, muscle, fetal brain, spinal cord and fetal liver. Isoform 3 is expressed in most normal tissues but is not detected in lung, spleen, testis, fetal brain, spinal cord and fetal liver. Isoform 7 is expressed in most normal tissues but is not detected in prostate, uterus, skeletal muscle and breast. Isoform 8 is detected only in colon, bone marrow, testis, fetal brain and intestine. Isoform 9 is expressed in most normal tissues but is not detected in brain, heart, lung, fetal liver, salivary gland, breast or intestine. Belongs to the p53 family. Note: This description may include information from UniProtKB.
Molecular Function: 14-3-3 protein binding; ATP-dependent DNA/DNA annealing activity; chromatin binding; cis-regulatory region sequence-specific DNA binding; copper ion binding; core promoter sequence-specific DNA binding; disordered domain specific binding; DNA binding; DNA-binding transcription activator activity, RNA polymerase II-specific; DNA-binding transcription factor activity; DNA-binding transcription factor activity, RNA polymerase II-specific; DNA-binding transcription repressor activity, RNA polymerase II-specific; enzyme binding; general transcription initiation factor binding; histone deacetylase binding; histone deacetylase regulator activity; identical protein binding; MDM2/MDM4 family protein binding; metal ion binding; molecular function activator activity; mRNA 3'-UTR binding; p53 binding; promoter-specific chromatin binding; protease binding; protein binding; protein heterodimerization activity; protein phosphatase 2A binding; protein self-association; protein-folding chaperone binding; receptor tyrosine kinase binding; RNA polymerase II cis-regulatory region sequence-specific DNA binding; RNA polymerase II transcription regulatory region sequence-specific DNA binding; RNA polymerase II-specific DNA-binding transcription factor binding; sequence-specific DNA binding; TFIID-class transcription factor complex binding; transcription cis-regulatory region binding; transcription coregulator binding; transmembrane transporter binding; ubiquitin protein ligase binding
Biological Process: apoptotic process; apoptotic signaling pathway; autophagy; B cell lineage commitment; bone marrow development; cardiac muscle cell apoptotic process; cardiac septum morphogenesis; cell cycle; cell population proliferation; cellular response to actinomycin D; cellular response to gamma radiation; cellular response to glucose starvation; cellular response to ionizing radiation; cellular response to reactive oxygen species; cellular response to stress; cellular response to UV; cellular response to UV-C; cellular senescence; central nervous system development; cerebellum development; chromosome organization; circadian behavior; circadian rhythm; determination of adult lifespan; DNA damage response; 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; double-strand break repair; embryo development ending in birth or egg hatching; embryonic organ development; entrainment of circadian clock by photoperiod; ER overload response; fibroblast proliferation; gastrulation; glial cell proliferation; glucose catabolic process to lactate via pyruvate; heart development; hematopoietic progenitor cell differentiation; hematopoietic stem cell differentiation; in utero embryonic development; intrinsic apoptotic signaling pathway by p53 class mediator; intrinsic apoptotic signaling pathway in response to DNA damage by p53 class mediator; intrinsic apoptotic signaling pathway in response to endoplasmic reticulum stress; intrinsic apoptotic signaling pathway in response to hypoxia; mitochondrial DNA repair; mitophagy; mitotic G1 DNA damage checkpoint signaling; mRNA transcription; multicellular organism growth; necroptotic process; negative regulation of apoptotic process; negative regulation of cell growth; negative regulation of cell population proliferation; negative regulation of DNA biosynthetic process; negative regulation of DNA replication; negative regulation of DNA-templated transcription; negative regulation of fibroblast proliferation; negative regulation of G1 to G0 transition; negative regulation of gene expression; negative regulation of glial cell proliferation; negative regulation of glucose catabolic process to lactate via pyruvate; negative regulation of miRNA processing; negative regulation of mitophagy; negative regulation of mitotic cell cycle; negative regulation of neuroblast proliferation; negative regulation of pentose-phosphate shunt; negative regulation of proteolysis; negative regulation of reactive oxygen species metabolic process; negative regulation of smooth muscle cell proliferation; negative regulation of stem cell proliferation; negative regulation of telomerase activity; negative regulation of transcription by RNA polymerase II; negative regulation of transforming growth factor beta receptor signaling pathway; neuroblast proliferation; neuron apoptotic process; nucleotide-excision repair; oligodendrocyte apoptotic process; oxidative stress-induced premature senescence; positive regulation of apoptotic process; positive regulation of cardiac muscle cell apoptotic process; positive regulation of cell cycle; positive regulation of cellular senescence; positive regulation of DNA-templated transcription; positive regulation of execution phase of apoptosis; positive regulation of gene expression; positive regulation of intrinsic apoptotic signaling pathway; positive regulation of leukocyte migration; positive regulation of miRNA transcription; positive regulation of mitochondrial membrane permeability; positive regulation of neuron apoptotic process; positive regulation of peptidyl-tyrosine phosphorylation; positive regulation of programmed necrotic cell death; positive regulation of reactive oxygen species metabolic process; positive regulation of release of cytochrome c from mitochondria; positive regulation of RNA polymerase II transcription preinitiation complex assembly; positive regulation of thymocyte apoptotic process; positive regulation of transcription by RNA polymerase II; positive regulation of transcription from RNA polymerase II promoter in response to endoplasmic reticulum stress; positive regulation of transcription from RNA polymerase II promoter in response to hypoxia; positive regulation of transcription from RNA polymerase II promoter in response to stress; programmed cell death; protein import into nucleus; protein localization; protein stabilization; protein tetramerization; protein-containing complex assembly; reactive oxygen species metabolic process; regulation of apoptotic process; regulation of cell cycle; regulation of cell cycle G2/M phase transition; regulation of cell population proliferation; regulation of cellular senescence; regulation of DNA damage response, signal transduction by p53 class mediator; regulation of DNA-templated transcription; regulation of fibroblast apoptotic process; regulation of intracellular pH; regulation of intrinsic apoptotic signaling pathway by p53 class mediator; regulation of mitochondrial membrane permeability involved in apoptotic process; regulation of mitotic cell cycle; regulation of neuron apoptotic process; regulation of thymocyte apoptotic process; regulation of tissue remodeling; regulation of transcription by RNA polymerase II; release of cytochrome c from mitochondria; replicative senescence; response to gamma radiation; response to inorganic substance; response to ischemia; response to oxidative stress; response to salt stress; response to UV; response to X-ray; response to xenobiotic stimulus; rhythmic process; rRNA transcription; signal transduction by p53 class mediator; somitogenesis; spermatogenesis; stem cell proliferation; T cell differentiation in thymus; T cell lineage commitment; T cell proliferation involved in immune response; thymocyte apoptotic process; transcription initiation-coupled chromatin remodeling; transforming growth factor beta receptor signaling pathway; tumor necrosis factor-mediated signaling pathway; type II interferon-mediated signaling pathway; viral process
