P53, Mutant (TRP53) Recombinant Protein

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. Mice deficient for this gene are developmentally normal but are susceptible to spontaneous tumors. Evidence to date shows that this gene contains one promoter, in contrast to alternative promoters of the human gene, and transcribes a few of splice variants which encode different isoforms, although the biological validity or the full-length nature of some variants has not been determined. [provided by RefSeq, Jul 2008]

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

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

Molecular Function: identical protein binding; protease binding; protein phosphatase 2A binding; metal ion binding; transcription factor binding; protein phosphatase 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; regulation of cell cycle; positive regulation of apoptosis; positive regulation of leukocyte migration; multicellular organismal development; positive regulation of transcription, DNA-dependent; programmed cell death; 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; cellular response to glucose starvation; protein localization; negative regulation of neuroblast proliferation; transforming growth factor beta receptor signaling pathway; 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; transcription, DNA-dependent; cell aging; chromatin assembly; positive regulation of cell cycle; 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; 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; 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; negative regulation of cell proliferation; embryonic development ending in birth or egg hatching; positive regulation of histone deacetylation; DNA damage response, signal transduction by p53 class mediator resulting in transcription of p21 class mediator; 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; negative regulation of proteolysis; mitochondrial DNA repair; in utero embryonic development; multicellular organism growth; B cell lineage commitment; cell cycle; regulation of cell proliferation; neuron apoptosis; T cell lineage commitment; nucleotide-excision repair; protein import into nucleus, translocation; DNA strand renaturation; negative regulation of cell growth; negative regulation of transforming growth factor beta receptor signaling pathway; response to DNA damage stimulus