背景介绍
cofactor:Binds 1 zinc ion per subunit.,disease:Defects in TP53 are a cause of choroid plexus papilloma [MIM:260500]. Choroid plexus papilloma is a slow-growing benign tumor of the choroid plexus that often invades the leptomeninges. In children it is usually in a lateral ventricle but in adults it is more often in the fourth ventricle. Hydrocephalus is common, either from obstruction or from tumor secretion of cerebrospinal fluid. If it undergoes malignant transformation it is called a choroid plexus carcinoma. Primary choroid plexus tumors are rare and usually occur in early childhood.,disease:Defects in TP53 are a cause of Li-Fraumeni syndrome (LFS) [MIM:151623]. LFS is an autosomal dominant familial cancer syndrome that in its classic form is defined by the existence of a proband affected by a sarcoma before 45 years with a first degree relative affected by any tumor before 45 years and another first degree relative with any tumor before 45 years or a sarcoma at any age. Other clinical definitions for LFS have been proposed (PubMed:8118819 and PubMed:8718514) and called Li-Fraumeni like syndrome (LFL). In these families affected relatives develop a diverse set of malignancies at unusually early ages. Four types of cancers account for 80% of tumors occurring in TP53 germline mutation carriers: breast cancers, soft tissue and bone sarcomas, brain tumors (astrocytomas) and adrenocortical carcinomas. Less frequent tumors include choroid plexus carcinoma or papilloma before the age of 15, rhabdomyosarcoma before the age of 5, leukemia, Wilms tumor, malignant phyllodes tumor, colorectal and gastric cancers.,disease:Defects in TP53 are a cause of lung cancer [MIM:211980].,disease:Defects in TP53 are a cause of one form of hereditary adrenocortical carcinoma (ADCC) [MIM:202300]. ADCC is a rare childhood tumor, representing about 0.4% of childhood tumors, with a high incidence of associated tumors. ADCC occurs with increased frequency in patients with the Beckwith-Wiedemann syndrome [MIM:130650] and is a component tumor in Li-Fraumeni syndrome [MIM:151623].,disease:Defects in TP53 are found in Barrett metaplasia; also known as Barrett esophagus. It is a condition in which the normally stratified squamous epithelium of the lower esophagus is replaced by a metaplastic columnar epithelium. The condition develops as a complication in approximately 10% of patients with chronic gastroesophageal reflux disease and predisposes to the development of esophageal adenocarcinoma.,disease:Defects in TP53 are involved in esophageal squamous cell carcinoma (ESCC) [MIM:133239]. ESCC is a tumor of the esophagus.,disease:Defects in TP53 are involved in head and neck squamous cell carcinomas (HNSCC) [MIM:275355].,disease:Defects in TP53 are involved in oral squamous cell carcinoma (OSCC). Cigarette smoke is a prime mutagenic agent in cancer of the aerodigestive tract.,disease:Defects in TP53 may be associated with nasopharyngeal carcinoma [MIM:161550]; also known as nasopharyngeal cancer.,disease:TP53 is found in increased amounts in a wide variety of transformed cells. TP53 is frequently mutated or inactivated in about 60% of cancers.,domain:The nuclear export signal acts as a transcriptional repression domain.,function:Acts as a tumor suppressor in many tumor types; induces growth arrest or apoptosis depending on the physiological circumstances and cell type. 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. One of the activated genes is an inhibitor of cyclin-dependent kinases. Apoptosis induction seems to be mediated either by stimulation of BAX and FAS antigen expression, or by repression of Bcl-2 expression.,function:Acts as a tumor suppressor in many tumor types; induces growth arrest or apoptosis depending on the physiological circumstances and cell type. 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. One of the activated genes is an inhibitor of cyclin-dependent kinases. Apoptosis induction seems to be mediated either by stimulation of BAX and FAS antigen expression, or by repression of Bcl-2 expression. Implicated in Notch signaling cross-over.,online information:P53 entry,online information:Somatic and germline TP53 mutations in human cancers,online information:The Singapore human mutation and polymorphism database,PTM:Acetylated. Acetylation of Lys-382 by CREBBP enhances transcriptional activity. Deacetylation of Lys-382 by SIRT1 impairs its ability to induce proapoptotic program and modulate cell senescence.,PTM:Demethylation of di-methylated Lys-370 by KDM1/LSD1 prevents interaction with TP53BP1 and represses TP53-mediated transcriptional activation.,PTM:Dephosphorylated by PP2A. SV40 small T antigen inhibits the dephosphorylation by the AC form of PP2A.,PTM:May be O-glycosylated in the C-terminal basic region. Studied in EB-1 cell line.,PTM:Monomethylated at Lys-372 by SETD7, leading to stabilize it and increase transcriptional activation. Monomethylated at Lys-370 by SMYD2, leading to decrease DNA-binding activity and subsequent transcriptional regulation activity. Lys-372 monomethylation prevents the interaction with SMYD2 and subsequenct monomethylation at Lys-370.,PTM:Phosphorylation on Ser residues mediates transcriptional activation. Phosphorylated by HIPK1 (By similarity). Phosphorylation at Ser-9 by HIPK4 increases repression activity on BIRC5 promoter. Phosphorylated on Thr-18 by VRK1, which may prevent the interaction with MDM2. Phosphorylated on Thr-55 by TAF1, which promotes MDM2-mediated degradation. Phosphorylated on Ser-46 by HIPK2 upon UV irradiation. Phosphorylation on Ser-46 is required for acetylation by CREBBP. Phosphorylated on Ser-392 following UV but not gamma irradiation. Phosphorylated upon DNA damage, probably by ATM or ATR. Phosphorylated on Ser-15 upon ultraviolet irradiation; which is enhanced by interaction with BANP.,PTM:Sumoylated by SUMO1.,PTM:Ubiquitinated by SYVN1, which leads to proteasomal degradation.,similarity:Belongs to the p53 family.,subcellular location:Interaction with BANP promotes nuclear localization.,subunit:Binds DNA as a homotetramer.,subunit:Interacts with AXIN1. Probably part of a complex consisting of TP53, HIPK2 and AXIN1 (By similarity). Binds DNA as a homotetramer. Interacts with histone acetyltransferases EP300 and methyltransferases HRMT1L2 and CARM1, and recruits them to promoters. In vitro, the interaction of TP53 with cancer-associated/HPV (E6) viral proteins leads to ubiquitination and degradation of TP53 giving a possible model for cell growth regulation. This complex formation requires an additional factor, E6-AP, which stably associates with TP53 in the presence of E6. Interacts (via C-terminus) with TAF1; when TAF1 is part of the TFIID complex. Interacts with ING4; this interaction may be indirect. Found in a complex with CABLES1 and TP73. Interacts with HIPK1, HIPK2, and P53DINP1. Interacts with WWOX. May interact with HCV core protein. Interacts with USP7 and SYVN1. Interacts with HSP90AB1. Interacts with CHD8; leading to recruit histone H1 and prevent transactivation activity (By similarity). Interacts with ARMC10, BANP, CDKN2AIP and E4F1. Interacts with YWHAZ; the interaction enhances P53 transcriptional activity. Phosphorylation of YWHAZ on 'Ser-58' inhibits this interaction. Interacts (via DNA-binding domain) with MAML1 (via N-terminus).,
功能
protein import into nucleus, translocation,?cell cycle checkpoint,?DNA damage checkpoint,?negative regulation of transcription from RNA polymerase II promoter,?regulation of cell growth,?in utero embryonic development,?cell activation,?release of cytochrome c from mitochondria,?cell activation during immune response,?lymphocyte activation during immune response,?T cell activation during immune response,?T cell proliferation during immune response,?B cell lineage commitment,?response to tumor cell,?T cell lineage commitment,?leukocyte activation during immune response,immune system development,?leukocyte differentiation,?DNA metabolic process,?regulation of DNA replication,?DNA repair,?base-excision repair,?nucleotide-excision repair,?double-strand break repair,?transcription,?transcription, DNA-dependent,?regulation of transcription, DNA-dependent,?regulation of transcription from RNA polymerase II promoter,protein complex assembly,?protein targeting,?protein import into nucleus,?mitochondrial transport,?cellular ion homeostasis,?regulation of pH,?intracellular protein transport,?nucleocytoplasmic transport,?apoptosis,?induction of apoptosis,?activation of caspase activity,?immune response,?response to osmotic stress,?response to DNA damage stimulus,?ER overload response,?ER-nuclear signaling pathway,?mitochondrion organization,?mitochondrial membrane organization,?cell cycle,?cell cycle arrest,?mitotic cell cycle checkpoint,?intracellular signaling cascade,?regulation of mitotic cell cycle,?gastrulation,?negative regulation of neuroblast proliferation,?aging,?cell aging,?protein localization,negative regulation of DNA replication,?cell death,?cell proliferation,?negative regulation of cell proliferation,?regulation of cell size,?induction of apoptosis by intracellular signals,?DNA damage response, signal transduction resulting in induction of apoptosis,?activation of caspase activity by cytochrome c,?apoptotic mitochondrial changes,?cellular response to starvation,?rRNA transcription,?response to radiation,?response to UV,?response to light stimulus,response to abiotic stimulus,?response to salt stress,?embryonic development ending in birth or egg hatching,negative regulation of biosynthetic process,?positive regulation of biosynthetic process,?response to extracellular stimulus,?response to X-ray,?response to ionizing radiation,?response to gamma radiation,?regulation of specific transcription from RNA polymerase II promoter,?positive regulation of specific transcription from RNA polymerase II promoter,?positive regulation of macromolecule biosynthetic process,?negative regulation of macromolecule biosynthetic process,?positive regulation of macromolecule metabolic process,?negative regulation of macromolecule metabolic process,?positive regulation of gene expression,?negative regulation of gene expression,?negative regulation of cell development,?regulation of cell death,?positive regulation of cell death,?positive regulation of peptidase activity,?programmed cell death,?induction of programmed cell death,?protein transport,?membrane organization,?death,?negative regulation of transcription,?protein import,?cellular homeostasis,?cell cycle process,cellular cation homeostasis,?cellular monovalent inorganic cation homeostasis,?hemopoiesis,?lymphocyte differentiation,?B cell differentiation,?T cell differentiation,?negative regulation of cell growth,?DNA damage response, signal transduction by p53 class mediator,?regulation of cellular pH,?negative regulation of cellular biosynthetic process,?positive regulation of cellular biosynthetic process,?DNA integrity checkpoint,?G1 DNA damage checkpoint,G1/S transition checkpoint,?response to nutrient levels,?cellular response to extracellular stimulus,?cellular response to nutrient levels,?regulation of cellular component size,?regulation of gene-specific transcription,?RNA biosynthetic process,?mononuclear cell proliferation,?T cell differentiation in the thymus,?protein localization in organelle,?cellular response to stress,?protein localization in nucleus,?cellular protein localization,?cellular response to UV,?response to endoplasmic reticulum stress,?regulation of growth,?T cell proliferation,?T cell activation,?B cell activation,?regulation of cell proliferation,?cellular response to glucose starvation,?response to drug,?homeostatic process,?response to starvation,?DNA damage response, signal transduction,?DNA damage response, signal transduction by p53 class mediator resulting in induction of apoptosis,?regulation of apoptosis,?chordate embryonic development,?positive regulation of apoptosis,?negative regulation of apoptosis,?regulation of programmed cell death,?positive regulation of programmed cell death,?negative regulation of programmed cell death,?positive regulation of catalytic activity,?negative regulation of catalytic activity,?positive regulation of gene-specific transcription,?positive regulation of caspase activity,regulation of caspase activity,?regulation of neuron apoptosis,?positive regulation of neuron apoptosis,macromolecular complex subunit organization,?negative regulation of molecular function,?positive regulation of molecular function,?cell fate commitment,?establishment of protein localization,?leukocyte activation,?regulation of transcription,?negative regulation of cell differentiation,?negative regulation of cell cycle,?negative regulation of cell size,?negative regulation of transcription, DNA-dependent,?positive regulation of transcription, DNA-dependent,negative regulation of growth,?negative regulation of nucleobase, nucleoside, nucleotide and nucleic acid metabolic process,?positive regulation of nucleobase, nucleoside, nucleotide and nucleic acid metabolic process,?positive regulation of transcription,?positive regulation of transcription from RNA polymerase II promoter,?lymphocyte activation,?lymphocyte proliferation,?regulation of mitochondrial membrane permeability,?intracellular transport,regulation of fibroblast proliferation,?negative regulation of fibroblast proliferation,?hemopoietic or lymphoid organ development,?embryonic morphogenesis,?chemical homeostasis,?regulation of neurogenesis,?negative regulation of neurogenesis,?ion homeostasis,?regulation of DNA metabolic process,?negative regulation of DNA metabolic process,regulation of helicase activity,?negative regulation of helicase activity,?nuclear transport,?nuclear import,?negative regulation of nitrogen compound metabolic process,?positive regulation of nitrogen compound metabolic process,regulation of RNA metabolic process,?negative regulation of RNA metabolic process,?positive regulation of RNA metabolic process,?protein oligomerization,?protein tetramerization,?chromosome organization,?regulation of hydrolase activity,?positive regulation of hydrolase activity,?negative regulation of hydrolase activity,?regulation of intracellular pH,?regulation of cell cycle,?regulation of nervous system development,?regulation of peptidase activity,?regulation of endopeptidase activity,?monovalent inorganic cation homeostasis,?cation homeostasis,?cellular chemical homeostasis,regulation of cell development,?negative regulation of cell death,?macromolecular complex assembly,?protein complex biogenesis,?leukocyte proliferation,?cellular macromolecule localization,
