p53

肿瘤蛋白p53
	PDB基于1TUP的渲染：P53与DNA结合[1]
有效结构
PDB	直系同源检索：PDBe, RCSB
PDB查询代码列表
	1A1U、 1AIE、 1C26、 1DT7、 1GZH、 1H26、 1HS5、 1JSP、 1KZY、 1MA3、 1OLG、 1OLH、 1PES、 1PET、 1SAE、 1SAF、 1SAK、 1SAL、 1TSR、 1TUP、 1UOL、 1XQH、 1YC5、 1YCQ、 1YCR、 1YCS、 2AC0、 2ADY、 2AHI、 2ATA、 2B3G、 2BIM、 2BIN、 2BIO、 2BIP、 2BIQ、 2FEJ、 2FOJ、 2FOO、 2GS0、 2H1L、 2H2D、 2H2F、 2H4F、 2H4H、 2H4J、 2H59、 2J0Z、 2J10、 2J11、 2J1W、 2J1X、 2J1Y、 2J1Z、 2J20、 2J21、 2K8F、 2L14、 2LY4、 2OCJ、 2PCX、 2QVQ、 2QXA、 2QXB、 2QXC、 2VUK、 2WGX、 2X0U、 2X0V、 2X0W、 2XWR、 2YBG、 2Z5S、 2Z5T、 3D05、 3D06、 3D07、 3D08、 3D09、 3D0A、 3DAB、 3DAC、 3IGK、 3IGL、 3KMD、 3KZ8、 3LW1、 3PDH、 3Q01、 3Q05、 3Q06、 3SAK、 3TG5、 3TS8、 4AGL、 4AGM、 4AGN、 4AGO、 4AGP、 4AGQ
标识
代号	TP53; BCC7; LFS1; P53; TRP53
扩展标识	遗传学：191170 鼠基因：98834 同源基因：460 ChEMBL: 4096 GeneCards: TP53 Gene
基因本体论描述
分子功能	· 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; · RNA polymerase II transcription regulatory region sequence-specific DNA binding transcription factor activity involved in positive regulation of transcription; · protease binding; · p53 binding; · DNA binding; · chromatin binding; · damaged DNA binding; · sequence-specific DNA binding transcription factor activity; · copper ion binding; · protein binding; · ATP binding; · transcription factor binding; · zinc ion binding; · enzyme binding; · protein kinase binding; · receptor tyrosine kinase binding; · ubiquitin protein ligase binding; · histone deacetylase regulator activity; · histone acetyltransferase binding; · identical protein binding; · transcription regulatory region DNA binding; · protein heterodimerization activity; · protein N-terminus binding; · chaperone binding; · protein phosphatase 2A binding;
细胞成分	· chromatin; · nuclear chromatin; · nucleus; · nucleoplasm; · replication fork; · transcription factor TFIID complex; · chromatin assembly complex; · nucleolus; · cytoplasm; · mitochondrion; · endoplasmic reticulum; · cytosol; · nuclear matrix; · nuclear body; · PML body; · protein complex;
生物过程	· protein import into nucleus、 translocation; · cell cycle checkpoint; · negative regulation of transcription from RNA polymerase II promoter; · DNA strand renaturation; · in utero embryonic development; · somitogenesis; · release of cytochrome c from mitochondria; · T cell proliferation involved in immune response; · B cell lineage commitment; · T cell lineage commitment; · base-excision repair; · nucleotide-excision repair; · double-strand break repair; · regulation of transcription、 DNA-dependent; · protein complex assembly; · apoptotic process; · induction of apoptosis; · response to DNA damage stimulus; · 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 transcription of p21 class mediator; · ER overload response; · cell cycle arrest; · transforming growth factor beta receptor signaling pathway; · Ras protein signal transduction; · multicellular organismal development; · gastrulation; · negative regulation of neuroblast proliferation; · central nervous system development; · cell aging; · blood coagulation; · protein localization; · negative regulation of DNA replication; · cell proliferation; · negative regulation of cell proliferation; · determination of adult lifespan; · rRNA transcription; · response to salt stress; · response to X-ray; · response to gamma radiation; · virus-host interaction; · cell differentiation; · negative regulation of cell growth; · DNA damage response、 signal transduction by p53 class mediator; · negative regulation of transforming growth factor beta receptor signaling pathway; · positive regulation of histone deacetylation; · mitotic cell cycle G1/S transition DNA damage checkpoint; · positive regulation of protein oligomerization; · T cell differentiation in thymus; · cellular protein localization; · cellular response to UV; · multicellular organism growth; · cellular response to drug; · cellular response to glucose starvation; · intrinsic apoptotic signaling pathway in response to DNA damage by p53 class mediator; · regulation of apoptotic process; · positive regulation of apoptotic process; · negative regulation of apoptotic process; · positive regulation of neuron apoptotic process; · negative regulation of transcription、 DNA-dependent; · positive regulation of transcription、 DNA-dependent; · positive regulation of transcription from RNA polymerase II promoter; · response to antibiotic; · regulation of mitochondrial membrane permeability; · negative regulation of fibroblast proliferation; · positive regulation of peptidyl-tyrosine phosphorylation; · negative regulation of helicase activity; · protein tetramerization; · chromosome organization; · neuron apoptotic process; · positive regulation of thymocyte apoptotic process; · positive regulation of cell cycle arrest; · cellular response to hypoxia; · cellular response to ionizing radiation; · mitotic cell cycle arrest; · intrinsic apoptotic signaling pathway by p53 class mediator; · positive regulation of release of cytochrome c from mitochondria; · positive regulation of cell aging; · replicative senescence; · oxidative stress-induced premature senescence; · intrinsic apoptotic signaling pathway; · positive regulation of reactive oxygen species metabolic process; · positive regulation of intrinsic apoptotic signaling pathway;
	Sources: Amigo / QuickGO
RNA表达模式
	更多表达数据
直系同源体

p53是一系列被称为腫瘤抑制蛋白（也稱為p53蛋白或p53腫瘤蛋白）的同源异构蛋白的统称。由TP53（人体）及Trp53（老鼠）基因编码。该蛋白是最早发现的肿瘤抑制基因所编码的蛋白之一。p53蛋白能調節細胞週期，促使細胞出現凋亡或細胞衰老（cell senescence）等現象，从而避免细胞癌变發生。p53蛋白能保持基因組的穩定性，避免或减少突變的發生。因此被稱為基因組守護者。

p53得名于1979年，因为其的分子量於SDS凝膠電泳中測得約為53kDa。不过依據胺基酸序列进行計算后发现p53蛋白的分子量應為43.7kDa.兩者所測得之分子量差別是因为该蛋白中存在大量的脯胺酸殘基，減緩了其在SDS膠電泳中的遷移速度。而此遷移速度減緩的效應在跨物種的p53蛋白皆已被觀察，如人類，嚙齒動物，青蛙和魚類。

目前在人体内发现的p53同源异构蛋白有15种；另外由於FOXO4可和p53結合以促進細胞衰老之故[2]，因此一些和FOXO4有競爭效應的胜肽，可藉由將p53屏除於細胞核之外而成為返老藥（Senolytic）。[2]

功能

p53蛋白在避免癌症發生機制上扮演重要的角色，例如，細胞凋亡 (apoptosis) 、細胞衰老（cell senescence）、基因組穩定性 (genetic stability) 、抑制血管新生 (angiogenesis)。 p53蛋白通過下列之機構達成避免癌症發生:

當DNA受損時，p53蛋白能活化DNA修復蛋白 (DNA repair proteins)。
p53蛋白能抑制細胞生長,通过使细胞周期停留於G₁/S的節律點上，以達成DNA損壞辨識。 (若能將細胞於此節律點上停留夠久，DNA修复蛋白將有更充裕的時間修復DNA損壞部位，並繼續細胞的生長週期。)
若細胞的DNA受損已不能修復，p53蛋白能起始細胞凋亡程序，避免擁有不正常遺傳資訊的細胞繼續分裂生長。

活化的p53蛋白能接合於DNA，促使多個基因表現，包括基因WAF1/CIP1，其為p21蛋白之編碼基因。 p21 (WAF1)接合於G₁-S/CDK (CDK2) 和S/CDK複合體 (此蛋白在G₁/S細胞週期節律點上有重要功能) 以抑制該複合體的活性。當p21蛋白 (WAF1) 與CDK2形成複合體時，細胞將無法進入到細胞分裂的階段。而突變後的p53蛋白將可能喪失與DNA形成有效結合的能力，造成p21蛋白將無法形成，以發出停止細胞分裂的信號。因此，受損細胞將不受控制的進行細胞分裂，最終形成腫瘤。根據最近的研究，p53蛋白與RB1程序經由p14ARF蛋白相互調節的可能性更加提高。

調節

p53蛋白藉由許多不同的壓力形式而激發其活性，其中包括但不僅僅侷限於DNA損傷 (包括 UV, IR或化學物質如過氧化氫 (hydrogen peroxide)所造成的損傷)，氧化壓力 (oxidative stress)，滲透壓力 (osmotic stress)，核糖核苷酸缺乏 (nucleotide depletion) 和喪失調節癌基因表現能力。這些活性激發可由兩個主要的事件得出。首先，在受到壓力的細胞中，p53蛋白的半衰期 (half-life) 會突然的增加，造成p53蛋白在細胞中的累積。再來則是構型變化 (conformational change) 使得p53蛋白被激發成為轉錄調節因子 (transcription regulator)。

参考文献

Y. Cho, S. Gorina, P. D. Jeffrey, N. P. Pavletich. . Science (New York, N.Y.). 1994-07-15, 265 (5170): 346–355 [2019-05-26]. ISSN 0036-8075. PMID 8023157.
Baar, Marjolein P.; Brandt, Renata M.C.; Putavet, Diana A.; Klein, Julian D.D.; Derks, Kasper W.J.; Bourgeois, Benjamin R.M.; Stryeck, Sarah; Rijksen, Yvonne; van Willigenburg, Hester; Feijtel, Danny A.; van der Pluijm, Ingrid; Essers, Jeroen; van Cappellen, Wiggert A.; van IJcken, Wilfred F.; Houtsmuller, Adriaan B.; Pothof, Joris; de Bruin, Ron W.F.; Madl, Tobias; Hoeijmakers, Jan H.J.; Campisi, Judith; de Keizer, Peter L.J. . Cell. March 2017, 169 (1): 132–147.e16. PMC 5556182. PMID 28340339. doi:10.1016/j.cell.2017.02.031.

外部链接

Lane Group at the Institute of Molecular and Cell Biology (IMCB), Singapore. p53 Knowledgebase [archived 2006-01-03; cited 2008-04-06].
GeneReviews/NCBI/NIH/UW entry on Li-Fraumeni Syndrome 页面存档备份，存于
TUMOR PROTEIN p53 页面存档备份，存于 @ OMIM
p53 页面存档备份，存于 @ The Atlas of Genetics and Cytogenetics in Oncology and Haematology
TP53 Gene 页面存档备份，存于 @ GeneCards
p53 News provided by insciences organisation
David S. Goodsell. RCSB Protein Data Bank. p53 Tumor Suppressor; 2002-07-01 [archived 2008-02-19; cited 2008-04-06].
Thierry Soussi. p53 Web Site [archived 2012-05-15; cited 2008-04-0 6].
The George Pantziarka TP53 Trust 页面存档备份，存于 A support group from the UK for sufferers of Li-Fraumeni Syndrome or other TP53-related disorders
IARC TP53 Somatic Mutations database 页面存档备份，存于 maintained at IARC, Lyon, by Magali Olivier

参见

肿瘤抑制基因

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[1] Y. Cho, S. Gorina, P. D. Jeffrey, N. P. Pavletich. . Science (New York, N.Y.). 1994-07-15, 265 (5170): 346–355 [2019-05-26]. ISSN 0036-8075. PMID 8023157.

[pmid28340339-2] Baar, Marjolein P.; Brandt, Renata M.C.; Putavet, Diana A.; Klein, Julian D.D.; Derks, Kasper W.J.; Bourgeois, Benjamin R.M.; Stryeck, Sarah; Rijksen, Yvonne; van Willigenburg, Hester; Feijtel, Danny A.; van der Pluijm, Ingrid; Essers, Jeroen; van Cappellen, Wiggert A.; van IJcken, Wilfred F.; Houtsmuller, Adriaan B.; Pothof, Joris; de Bruin, Ron W.F.; Madl, Tobias; Hoeijmakers, Jan H.J.; Campisi, Judith; de Keizer, Peter L.J. . Cell. March 2017, 169 (1): 132–147.e16. PMC 5556182. PMID 28340339. doi:10.1016/j.cell.2017.02.031.