P53 Tumor Suppressor Protein (TP53) Antibody – Mouse Monoclonal

This gene encodes a tumor suppressor protein containing transcriptional activation, DNA binding, and oligomerization domains. The encoded protein responds to diverse cellular stresses to regulate expression of target genes, thereby inducing cell cycle arrest, apoptosis, senescence, DNA repair, or changes in metabolism. Mutations in this gene are associated with a variety of human cancers, including hereditary cancers such as Li-Fraumeni syndrome. Alternative splicing of this gene and the use of alternate promoters result in multiple transcript variants and isoforms. Additional isoforms have also been shown to result from the use of alternate translation initiation codons from identical transcript variants (PMIDs: 12032546, 20937277). [provided by RefSeq, Dec 2016]

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: Motility/polarity/chemotaxis; Tumor suppressor; Nuclear receptor co-regulator; DNA-binding; Transcription factor; Activator

Chromosomal Location of Human Ortholog: 17p13.1

Cellular Component: PML body; transcription factor TFIID complex; protein complex; nuclear matrix; mitochondrion; endoplasmic reticulum; replication fork; cytosol; nucleoplasm; nuclear body; mitochondrial matrix; nuclear chromatin; cytoplasm; nucleolus; nucleus; chromatin

Molecular Function: identical protein binding; protease binding; protein phosphatase 2A binding; zinc ion binding; p53 binding; protein N-terminus binding; receptor tyrosine kinase binding; protein kinase binding; protein phosphatase binding; transcription factor binding; histone acetyltransferase binding; protein binding; histone deacetylase regulator activity; copper ion binding; enzyme binding; DNA binding; protein heterodimerization activity; ubiquitin protein ligase binding; chaperone binding; damaged DNA binding; chromatin binding; transcription factor activity; ATP binding

Biological Process: viral reproduction; positive regulation of apoptosis; multicellular organismal development; positive regulation of transcription, DNA-dependent; 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; regulation of apoptosis; response to antibiotic; cellular response to glucose starvation; protein localization; negative regulation of neuroblast proliferation; base-excision repair; transforming growth factor beta receptor signaling pathway; cerebellum development; protein complex assembly; cell cycle arrest; ER overload response; response to X-ray; somitogenesis; release of cytochrome c from mitochondria; chromatin assembly; cell aging; circadian behavior; rRNA transcription; positive regulation of peptidyl-tyrosine phosphorylation; negative regulation of DNA replication; negative regulation of fibroblast proliferation; embryonic organ development; positive regulation of transcription from RNA polymerase II promoter; regulation of mitochondrial membrane permeability; negative regulation of transcription, DNA-dependent; regulation of tissue remodeling; negative regulation of apoptosis; transcription from RNA polymerase II promoter; G1 DNA damage checkpoint; DNA damage response, signal transduction by p53 class mediator; apoptosis; negative regulation of transcription from RNA polymerase II promoter; response to salt stress; entrainment of circadian clock by photoperiod; positive regulation of protein oligomerization; 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; positive regulation of neuron apoptosis; double-strand break repair; response to gamma radiation; cell differentiation; DNA damage response, signal transduction by p53 class mediator resulting in induction of apoptosis; protein tetramerization; mitochondrial DNA repair; Notch signaling pathway; in utero embryonic development; multicellular organism growth; B cell lineage commitment; cell proliferation; neuron apoptosis; T cell lineage commitment; negative regulation of helicase activity; nucleotide-excision repair; protein import into nucleus, translocation; Ras protein signal transduction; DNA strand renaturation; negative regulation of cell growth; blood coagulation; negative regulation of transforming growth factor beta receptor signaling pathway; response to DNA damage stimulus

Disease: Papilloma Of Choroid Plexus; Pancreatic Cancer; Nasopharyngeal Carcinoma; Breast Cancer; Li-fraumeni Syndrome 1; Osteogenic Sarcoma; Colorectal Cancer; Glioma Susceptibility 1; Adrenocortical Carcinoma, Hereditary; Basal Cell Carcinoma, Susceptibility To, 7; Hepatocellular Carcinoma