TP53 Antibody – Rabbit Polyclonal

This gene encodes tumor protein p53, which responds to diverse cellular stresses to regulate target genes that induce cell cycle arrest, apoptosis, senescence, DNA repair, or changes in metabolism. p53 protein is expressed at low level in normal cells and at a high level in a variety of transformed cell lines, where it's believed to contribute to transformation and malignancy. p53 is a DNA-binding protein containing transcription activation, DNA-binding, and oligomerization domains. It is postulated to bind to a p53-binding site and activate expression of downstream genes that inhibit growth and/or invasion, and thus function as a tumor suppressor. Mutants of p53 that frequently occur in a number of different human cancers fail to bind the consensus DNA binding site, and hence cause the loss of tumor suppressor activity. Alterations of this gene occur not only as somatic mutations in human malignancies, but also as germline mutations in some cancer-prone families with Li-Fraumeni syndrome. Multiple p53 variants due to alternative promoters and multiple alternative splicing have been found. These variants encode distinct isoforms, which can regulate p53 transcriptional activity. [provided by RefSeq]

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

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; chromatin; nucleus

Molecular Function: identical protein binding; protease binding; zinc ion binding; protein phosphatase 2A 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; copper ion binding; histone deacetylase regulator activity; 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; positive regulation of transcription, DNA-dependent; 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; 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; release of cytochrome c from mitochondria; somitogenesis; chromatin assembly; cell aging; circadian behavior; rRNA transcription; positive regulation of peptidyl-tyrosine phosphorylation; negative regulation of fibroblast proliferation; negative regulation of DNA replication; 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; G1 DNA damage checkpoint; transcription from RNA polymerase II promoter; 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; double-strand break repair; positive regulation of neuron apoptosis; 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; B cell lineage commitment; multicellular organism growth; cell proliferation; T cell lineage commitment; neuron apoptosis; 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; negative regulation of transforming growth factor beta receptor signaling pathway; blood coagulation; 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