p53

P53
已知的結構
PDB	直系同源搜索: PDBe RCSB
PDBID列表
	4QO1、1A1U、1AIE、1C26、1DT7、1GZH、1H26、1HS5、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、2MEJ、2MWO、2MWP、2MZD、2OCJ、2PCX、2RUK、2VUK、2WGX、2X0U、2X0V、2X0W、2XWR、2YBG、2YDR、2Z5S、2Z5T、3D05、3D06、3D07、3D08、3D09、3D0A、3DAB、3DAC、3IGK、3IGL、3KMD、3KZ8、3LW1、3OQ5、3PDH、3Q01、3Q05、3Q06、3SAK、3TG5、3TS8、3ZME、4AGL、4AGM、4AGN、4AGO、4AGP、4AGQ、4BUZ、4BV2、4HFZ、4HJE、4IBQ、4IBS、4IBT、4IBU、4IBV、4IBW、4IBY、4IBZ、4IJT、4KVP、4LO9、4LOE、4LOF、4MZI、4MZR、4X34、4ZZJ、5AOL、5ABA、5AOK、2MWY、5A7B、5AOJ、5AOI、5ECG、5AB9、4FZ3、4RP6、4XR8、5AOM、4RP7、5HOU、5HP0、5HPD、5LGY、5G4M、5G4O、5G4N、5BUA
識別號
别名	TP53；, BCC7, LFS1, P53, TRP53, tumor protein p53, BMFS5, Genes, p53
外部ID	OMIM：191170 MGI：98834 HomoloGene：460 GeneCards：TP53
相關疾病
	基底細胞癌（BCC）、头颈部鳞状细胞癌、李-佛美尼症候群、Li-Fraumeni syndrome 1、B細胞慢性淋巴性白血病、liver carcinoma、急性骨髓性白血病、breast adenocarcinoma、gastric adenocarcinoma、肺腺癌、骨肉瘤、prostate adenocarcinoma、lung small cell carcinoma、肺鱗狀上皮癌、large intestine cancer、pancreatic adenocarcinoma
基因位置（人类）
染色体	17號染色體
终止	7,687,538 bp
基因位置（小鼠）
染色体	小鼠11号染色体
终止	69,482,699 bp
RNA表达模式
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	查阅更多表达数据
基因本體
分子功能	• protein N-terminus binding; • DNA结合转录因子活性; • 蛋白質自締合; • core promoter sequence-specific DNA binding; • DNA-binding transcription factor activity, RNA polymerase II-specific; • protein phosphatase binding; • ATP結合; • 转录因子结合; • 金屬離子結合; • protein phosphatase 2A binding; • 酶结合; • 鋅離子結合; • chromatin binding; • 蛋白酶結合; • damaged DNA binding; • 血浆蛋白结合; • histone acetyltransferase binding; • copper ion binding; • protein kinase binding; • chaperone binding; • DNA-binding transcription activator activity, RNA polymerase II-specific; • receptor tyrosine kinase binding; • p53 binding; • 相同蛋白质结合; • protein heterodimerization activity; • 泛素蛋白连接酶结合; • RNA polymerase II transcription regulatory region sequence-specific DNA binding; • DNA结合; • RNA polymerase II cis-regulatory region sequence-specific DNA binding; • TFIID-class transcription factor complex binding; • mRNA 3'-UTR binding; • histone deacetylase binding; • 无序域特异性结合; • promoter-specific chromatin binding; • histone deacetylase regulator activity; • protein homodimerization activity; • MDM2/MDM4 family protein binding;
細胞組分	• 細胞質; • 線粒體; • 细胞核; • nuclear body; • transcription factor TFIID complex; • nuclear matrix; • replication fork; • 核仁; • 内质网; • 核质; • 线粒体基质; • PML body; • 细胞质基质; • 胞內; • 轉錄調節複合物; • 大分子复合体; • site of double-strand break;
生物學過程	• positive regulation of histone deacetylation; • DNA damage response, signal transduction by p53 class mediator resulting in cell cycle arrest; • rhythmic process; • replicative senescence; • negative regulation of telomerase activity; • oligodendrocyte apoptotic process; • cellular response to DNA damage stimulus; • intrinsic apoptotic signaling pathway; • positive regulation of neuron apoptotic process; • regulation of mitochondrial membrane permeability; • positive regulation of reactive oxygen species metabolic process; • cellular response to ionizing radiation; • positive regulation of thymocyte apoptotic process; • negative regulation of helicase activity; • 細胞週期; • Ras protein signal transduction; • 細胞增殖; • cellular response to hypoxia; • negative regulation of cell population proliferation; • 核苷酸切除修复; • cellular response to glucose starvation; • regulation of transcription, DNA-templated; • response to antibiotic; • transcription, DNA-templated; • ER overload response; • positive regulation of transcription, DNA-templated; • negative regulation of cell growth; • intrinsic apoptotic signaling pathway by p53 class mediator; • positive regulation of peptidyl-tyrosine phosphorylation; • viral process; • response to gamma radiation; • negative regulation of fibroblast proliferation; • positive regulation of intrinsic apoptotic signaling pathway; • 细胞分化; • determination of adult lifespan; • positive regulation of transcription from RNA polymerase II promoter in response to endoplasmic reticulum stress; • cellular response to UV; • DNA damage response, signal transduction by p53 class mediator; • negative regulation of apoptotic process; • protein tetramerization; • oxidative stress-induced premature senescence; • positive regulation of release of cytochrome c from mitochondria; • circadian behavior; • negative regulation of transcription, DNA-templated; • protein localization; • intrinsic apoptotic signaling pathway in response to DNA damage by p53 class mediator; • positive regulation of execution phase of apoptosis; • multicellular organism development; • positive regulation of protein insertion into mitochondrial membrane involved in apoptotic signaling pathway; • positive regulation of gene expression; • mitotic G1 DNA damage checkpoint signaling; • positive regulation of protein oligomerization; • positive regulation of apoptotic process; • entrainment of circadian clock by photoperiod; • response to X-ray; • positive regulation of transcription by RNA polymerase II; • base-excision repair; • DNA damage response, signal transduction by p53 class mediator resulting in transcription of p21 class mediator; • regulation of cell cycle G2/M phase transition; • proteasome-mediated ubiquitin-dependent protein catabolic process; • regulation of signal transduction by p53 class mediator; • 细胞凋亡; • transcription by RNA polymerase II; • positive regulation of protein export from nucleus; • 细胞程序性死亡; • regulation of apoptotic process; • protein deubiquitination; • phosphatidylinositol-mediated signaling; • negative regulation of transcription by RNA polymerase II; • 自噬; • mRNA transcription; • cytokine-mediated signaling pathway; • positive regulation of RNA polymerase II transcription preinitiation complex assembly; • RNA polymerase II preinitiation complex assembly; • protein homotetramerization; • protein-containing complex assembly; • cellular response to gamma radiation; • signal transduction by p53 class mediator; • cellular response to actinomycin D; • positive regulation of pri-miRNA transcription by RNA polymerase II; • positive regulation of production of miRNAs involved in gene silencing by miRNA; • in utero embryonic development; • somitogenesis; • release of cytochrome c from mitochondria; • hematopoietic progenitor cell differentiation; • T cell proliferation involved in immune response; • B cell lineage commitment; • T cell lineage commitment; • response to ischemia; • double-strand break repair; • regulation of transcription by RNA polymerase II; • protein import into nucleus; • response to oxidative stress; • transforming growth factor beta receptor signaling pathway; • 原腸胚形成; • negative regulation of neuroblast proliferation; • central nervous system development; • 心脏发育; • 昼夜节律; • negative regulation of DNA replication; • rRNA transcription; • response to UV; • response to salt stress; • embryo development ending in birth or egg hatching; • negative regulation of gene expression; • positive regulation of cardiac muscle cell apoptotic process; • cerebellum development; • negative regulation of transforming growth factor beta receptor signaling pathway; • T cell differentiation in thymus; • regulation of tissue remodeling; • multicellular organism growth; • positive regulation of mitochondrial membrane permeability; • positive regulation of transcription from RNA polymerase II promoter in response to stress; • regulation of cell population proliferation; • mitochondrial DNA repair; • regulation of DNA damage response, signal transduction by p53 class mediator; • regulation of neuron apoptotic process; • negative regulation of proteolysis; • negative regulation of mitotic cell cycle; • bone marrow development; • embryonic organ development; • protein stabilization; • chromosome organization; • neuron apoptotic process; • regulation of cell cycle; • hematopoietic stem cell differentiation; • interferon-gamma-mediated signaling pathway; • cardiac septum morphogenesis; • positive regulation of transcription from RNA polymerase II promoter in response to hypoxia; • positive regulation of programmed necrotic cell death; • intrinsic apoptotic signaling pathway in response to endoplasmic reticulum stress; • regulation of thymocyte apoptotic process; • 程序性坏死; • cellular response to UV-C; • negative regulation of mitophagy; • regulation of mitochondrial membrane permeability involved in apoptotic process; • regulation of intrinsic apoptotic signaling pathway by p53 class mediator; • negative regulation of production of miRNAs involved in gene silencing by miRNA; • negative regulation of glucose catabolic process to lactate via pyruvate; • intrinsic apoptotic signaling pathway in response to hypoxia; • regulation of fibroblast apoptotic process; • negative regulation of reactive oxygen species metabolic process; • regulation of cellular senescence;
	Sources:Amigo / QuickGO
直系同源
	7157
	22059
	ENSG00000141510
	ENSMUSG00000059552
	P04637
	P02340
NM_001276761; NM_000546; NM_001126112; NM_001126113; NM_001126114;
	NM_001126115; NM_001126116; NM_001126117; NM_001126118; NM_001276695; NM_001276696; NM_001276697; NM_001276698; NM_001276699; NM_001276760
	NM_001127233; NM_011640
NP_000537; NP_001119584; NP_001119585; NP_001119586; NP_001119587;
	NP_001119588; NP_001119589; NP_001119590; NP_001263624; NP_001263625; NP_001263626; NP_001263627; NP_001263628; NP_001263689; NP_001263690
	NP_001120705; NP_035770
	維基數據
檢視/編輯人類	檢視/編輯小鼠

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^[6]，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）。^[6]

功能编辑

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。

調節编辑

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)。

参考文献编辑

^ 與P53相關的疾病；在維基數據上查看/編輯參考.
^ ^2.0 ^2.1 ^2.2 GRCh38: Ensembl release 89: ENSG00000141510 - Ensembl, May 2017
^ ^3.0 ^3.1 ^3.2 GRCm38: Ensembl release 89: ENSMUSG00000059552 - Ensembl, May 2017
^ Human PubMed Reference:. National Center for Biotechnology Information, U.S. National Library of Medicine.
^ Mouse PubMed Reference:. National Center for Biotechnology Information, U.S. National Library of Medicine.
^ ^6.0 ^6.1 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. Targeted Apoptosis of Senescent Cells Restores Tissue Homeostasis in Response to Chemotoxicity and Aging. Cell. March 2017, 169 (1): 132–147.e16. PMC 5556182  . PMID 28340339. doi:10.1016/j.cell.2017.02.031.

外部链接编辑

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，存于互联网档案馆）
TUMOR PROTEIN p53（页面存档备份，存于互联网档案馆） @ OMIM
p53（页面存档备份，存于互联网档案馆） @ The Atlas of Genetics and Cytogenetics in Oncology and Haematology
TP53 Gene（页面存档备份，存于互联网档案馆） @ 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，存于互联网档案馆） 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，存于互联网档案馆） maintained at IARC, Lyon, by Magali Olivier

参见编辑

肿瘤抑制基因

[1] 與P53相關的疾病；在維基數據上查看/編輯參考.

[refGRCh38Ensembl-2] 2.0 ^2.1 ^2.2 GRCh38: Ensembl release 89: ENSG00000141510 - Ensembl, May 2017

[refGRCm38Ensembl-3] 3.0 ^3.1 ^3.2 GRCm38: Ensembl release 89: ENSMUSG00000059552 - Ensembl, May 2017

[4] Human PubMed Reference:. National Center for Biotechnology Information, U.S. National Library of Medicine.

[5] Mouse PubMed Reference:. National Center for Biotechnology Information, U.S. National Library of Medicine.

[pmid28340339-6] 6.0 ^6.1 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. Targeted Apoptosis of Senescent Cells Restores Tissue Homeostasis in Response to Chemotoxicity and Aging. Cell. March 2017, 169 (1): 132–147.e16. PMC 5556182  . PMID 28340339. doi:10.1016/j.cell.2017.02.031.

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p53

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