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TP53 (includes EG:22059) - tumor protein p53
Entrez Gene Name: tumor protein p53
Entrez GeneID: Human(7157)
, Mouse(22059), Rat(24842)
, Mouse(22059), Rat(24842) Synonyms: bbl, bfy, bhy, FLJ92943, LFS1, MGC112612, p44, P53, TP53 (includes EG:22059), TRP53
Gene Summary
- Human (7157): 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, Jul 2008]
- Mouse (22059): 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]
- Rat (24842): 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 is 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. Alternatively spliced transcript variants have been found for this gene, but the biological validity of the variants has not been determined. p53 pseudogenes have been found on chromosomes 9 and 18. [provided by RefSeq, Jul 2008]
Molecular Functions | Biological Process | Cellular Components | Protein Domains | Subcellular Locations | Pathways | Literature References | IPA Extras
Cell Regulation
Biological Process
activation of caspase activity by cytochrome c, aging, apoptosis, B cell lineage commitment, base-excision repair, blood coagulation, cell aging, cell cycle, cell cycle arrest, cell cycle checkpoint, cell differentiation, cell proliferation, cellular protein localization, cellular response to drug, cellular response to glucose starvation, cellular response to hypoxia, cellular response to ionizing radiation, cellular response to organic nitrogen, cellular response to UV, central nervous system development, chromosome organization, determination of adult lifespan, 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 induction of apoptosis, DNA damage response, signal transduction by p53 class mediator resulting in transcription of p21 class mediator, DNA strand renaturation, double-strand break repair, embryo development ending in birth or egg hatching, ER overload response, gastrulation, in utero embryonic development, induction of apoptosis, induction of apoptosis by intracellular signals, interspecies interaction between organisms, mitotic cell cycle G1/S transition DNA damage checkpoint, multicellular organism growth, multicellular organismal development, negative regulation of apoptosis, negative regulation of cell growth, negative regulation of cell proliferation, negative regulation of DNA biosynthetic process, negative regulation of DNA replication, negative regulation of fibroblast proliferation, negative regulation of helicase activity, negative regulation of neuroblast proliferation, negative regulation of smooth muscle cell proliferation, negative regulation of transcription from RNA polymerase II promoter, negative regulation of transcription, DNA-dependent, negative regulation of transforming growth factor beta receptor signaling pathway, nucleotide-excision repair, oxidative stress-induced premature senescence, positive regulation of apoptosis, positive regulation of cell aging, positive regulation of cell cycle, positive regulation of cell cycle arrest, positive regulation of histone deacetylation, positive regulation of leukocyte migration, positive regulation of neuron apoptosis, positive regulation of peptidyl-tyrosine phosphorylation, positive regulation of reactive oxygen species metabolic process, positive regulation of thymocyte apoptosis, positive regulation of transcription from RNA polymerase II promoter, positive regulation of transcription, DNA-dependent, protein complex assembly, protein import into nucleus, translocation, protein localization, protein tetramerization, Ras protein signal transduction, regulation of apoptosis, regulation of catalytic activity, regulation of cell cycle, regulation of cell proliferation, regulation of intracellular pH, regulation of mitochondrial membrane permeability, regulation of neuron apoptosis, regulation of transcription from RNA polymerase II promoter, regulation of transcription, DNA-dependent, release of cytochrome c from mitochondria, replicative senescence, response to amino acid stimulus, response to antibiotic, response to caffeine, response to chemical stimulus, response to cytokine stimulus, response to DNA damage stimulus, response to drug, response to gamma radiation, response to hyperoxia, response to inorganic substance, response to metal ion, response to organic cyclic compound, response to organic nitrogen, response to oxidative stress, response to retinoic acid, response to salt stress, response to UV, response to vitamin B3, response to X-ray, rRNA transcription, signal transduction by p53 class mediator resulting in induction of apoptosis, somitogenesis, T cell differentiation in thymus, T cell lineage commitment, T cell proliferation involved in immune response, transcription, DNA-dependent, transforming growth factor beta receptor signaling pathway, wound healing
Cellular Components
chromatin, cytoplasm, cytosol, endoplasmic reticulum, insoluble fraction, mitochondrion, nuclear body, nuclear chromatin, nuclear matrix, nucleolus, nucleoplasm, nucleus, PML body, protein complex, replication fork, soluble fraction, transcription factor complex, transcription factor TFIID complex
Literature References
- 21390126Pasqualucci L, Dominguez-Sola D, Chiarenza A, Fabbri G, Grunn A, Trifonov V, Kasper LH, Lerach S, Tang H, Ma J, Rossi D, Chadburn A, Murty VV, Mullighan CG, Gaidano G, Rabadan R, Brindle PK, Dalla-Favera R. Inactivating mutations of acetyltransferase genes in B-cell lymphoma.Nature 2011 Mar 10;471(7337):189-95
- 20837658Stegh AH, Brennan C, Mahoney JA, Forloney KL, Jenq HT, Luciano JP, Protopopov A, Chin L, Depinho RA. Glioma oncoprotein Bcl2L12 inhibits the p53 tumor suppressor.Genes Dev 2010 Oct 01;24(19):2194-204
- 18663127Muñoz-Fontela C, Macip S, Martínez-Sobrido L, Brown L, Ashour J, García-Sastre A, Lee SW, Aaronson SA. Transcriptional role of p53 in interferon-mediated antiviral immunity.J Exp Med 2008 Aug 04;205(8):1929-38
Molecular Functions
ATP binding, chaperone binding, chromatin binding, copper ion binding, damaged DNA binding, DNA binding, DNA strand annealing activity, double-stranded DNA binding, enzyme binding, histone acetyltransferase binding, histone deacetylase regulator activity, identical protein binding, MDM2 binding, metal ion binding, p53 binding, protease binding, protein binding, protein C-terminus binding, protein heterodimerization activity, protein kinase binding, protein N-terminus binding, protein phosphatase 2A binding, RNA polymerase II core promoter proximal region sequence-specific DNA binding transcription factor activity involved in positive regulation of transcription, RNA polymerase II transcription factor binding, sequence-specific DNA binding, sequence-specific DNA binding transcription factor activity, transcription factor binding, transcription regulatory region DNA binding, ubiquitin protein ligase binding, zinc ion binding
- SAPK/JNK Signaling
- Endometrial Cancer Signaling
- Role of PKR in Interferon Induction and Antiviral Response
- PI3K/AKT Signaling
- HER-2 Signaling in Breast Cancer
- Glioma Signaling
- Non-Small Cell Lung Cancer Signaling
- Cyclins and Cell Cycle Regulation
- Melanoma Signaling
- MIF Regulation of Innate Immunity
- Basal Cell Carcinoma Signaling
- Glioblastoma Multiforme Signaling
- Myc Mediated Apoptosis Signaling
- Hereditary Breast Cancer Signaling
- Breast Cancer Regulation by Stathmin1
- Telomerase Signaling
- Ovarian Cancer Signaling
- Role of BRCA1 in DNA Damage Response
- NGF Signaling
- Aryl Hydrocarbon Receptor Signaling
- Role of NANOG in Mammalian Embryonic Stem Cell Pluripotency
- Colorectal Cancer Metastasis Signaling
- Huntington's Disease Signaling
- Molecular Mechanisms of Cancer
- Role of Oct4 in Mammalian Embryonic Stem Cell Pluripotency
- ATM Signaling
- Apoptosis Signaling
- Role of Tissue Factor in Cancer
- Small Cell Lung Cancer Signaling
- Inhibition of Angiogenesis by TSP1
- HIF1α Signaling
- Wnt/β-catenin Signaling
- Chronic Myeloid Leukemia Signaling
- Induction of Apoptosis by HIV1
- Amyotrophic Lateral Sclerosis Signaling
- Bladder Cancer Signaling
- Hypoxia Signaling in the Cardiovascular System
- Cell Cycle: G1/S Checkpoint Regulation
- Role of CHK Proteins in Cell Cycle Checkpoint Control
- p53 Signaling
- Pancreatic Adenocarcinoma Signaling
- Cell Cycle: G2/M DNA Damage Checkpoint Regulation
- Thyroid Cancer Signaling
- Prostate Cancer Signaling
Protein Domains
A/B region, acetylation site, acidic domain, activation domain, activation domain AD1, AD1 domain, AD2 domain, ATM phosphorylation site, ATP binding, basic domain, beta strand or sheet, Box I domain, BRCA1-binding domain, C-terminal oligomerization domain, Casein Kinase 2 beta binding domain, central domain, chaperone binding, chromatin binding, copper ion binding, core domain, functional, core domain, structural, cytoplasmic sequestration domain, DNA binding, DNA binding domain, DNA strand annealing protein, docking domain, enzyme binding, extreme C-terminal domain, histone acetyltransferase binding, histone deacetylase regulator, homo-oligomerization domain, HPV-16 E2 protein binding domain, identical protein binding, Jnk-binding domain, loop-sheet-helix domain, LXXLL motif, lysine rich domain, Mdm2 protein binding domain, minimal transactivation domain, N-terminal transactivation domain, NDB domain, negative regulatory domain, nuclear export signal, nuclear localization sequence, oligomerization domain, p300/cbp binding domain, p53 core domain, P53 DNA-binding domain, P53 tetramerisation motif, P53 transactivation motif, phosphorylation site, PML binding domain, polyproline motif, proline rich domain, protease binding, protein binding, protein C-terminus binding, protein heterodimerization, protein kinase binding, protein N-terminus binding, PXXP motif, regulatory domain, replication protein A binding domain, S100B binding domain, serine phosphorylation site, Sh3 domain binding motif, TBP binding domain, tetramerization domain, transcription activation domain, transcription factor, transcription factor binding, transcription regulator, transcription repression domain, ubiquitin protein ligase binding, zinc finger domain, zinc ion binding
Subcellular Locations
centrosome, chromatin, Cytoplasm, cytoplasmic aggregates, cytoplasmic fraction, cytoplasmic particles, cytosol, cytosolic fraction, detergent-soluble fraction, DNA replication foci, insoluble fractions, metaphase plate, microtubules, mitochondria, mitoplasts, mitotic spindle, nuclear bodies, nuclear chromatin, nuclear foci, nuclear fraction, nuclear matrix, nuclear speckles, nucleoli, nucleoplasm, Nucleus, perinuclear body, perinuclear region, perinuclear space, Plasma Membrane, PML nuclear bodies, replication fork, soluble fraction