p53

P53
已知的结构
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
识别号
别名	TP53；, BCC7, LFS1, P53, TRP53, tumor protein p53, BMFS5, Genes, p53
外部ID	OMIM：191170 MGI：98834 HomoloGene：460 GeneCards：TP53
相关疾病
	基底细胞癌（BCC）、头颈部鳞状细胞癌、李-佛美尼症候群、Li-Fraumeni syndrome 1、B细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、肺鳞状上皮癌、large intestine cancer、pancreatic adenocarcinoma[1]
基因位置（人类）
染色体	17号染色体[2]
终止	7,687,538 bp[2]
基因位置（小鼠）
染色体	小鼠11号染色体[3]
终止	69,482,699 bp[3]
RNA表达模式
	; ;
	查阅更多表达数据
基因本体
分子功能	• protein N-terminus binding; • DNA结合转录因子活性; • 蛋白质自缔合; • core promoter sequence-specific DNA binding; • DNA-binding transcription factor activity, RNA polymerase II-specific; • protein phosphatase binding; • ATP结合; • 转录因子结合; • 金属离子结合; • protein phosphatase 2A binding; • 酶结合; • 锌离子结合; • chromatin binding; • 蛋白酶结合; • 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;
细胞组分	• 细胞质; • 线粒体; • 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; • 胞内; • 转录调节复合物; • 大分子复合体; • site of double-strand break;
生物学过程	• 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; • 细胞周期; • Ras protein signal transduction; • 细胞增殖; • 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; • 细胞进程性死亡; • 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; • 原肠胚形成; • 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; • 进程性坏死; • 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
	维基数据

p53是一系列被称为肿瘤抑制蛋白（也称为p53蛋白或p53肿瘤蛋白）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蛋白能调节细胞周期，促使细胞出现凋亡或细胞衰老（cell senescence）等现象，从而避免细胞癌变发生。p53蛋白能保持基因组的稳定性，避免或减少突变的发生。因此被称为基因组守护者。

p53得名于1979年，因为其的分子量于SDS凝胶电泳中测得约为53kDa。不过依据胺基酸串行进行计算后发现p53蛋白的分子量应为43.7kDa.两者所测得之分子量差别是因为该蛋白中存在大量的脯胺酸残基，减缓了其在SDS胶电泳中的迁移速度。而此迁移速度减缓的效应在跨物种的p53蛋白皆已被观察，如人类，啮齿动物，青蛙和鱼类。

目前在人体内发现的p53同源异构蛋白有15种；另外由于FOXO4可和p53结合以促进细胞衰老之故[6]，因此一些和FOXO4有竞争效应的胜肽，可借由将p53屏除于细胞核之外而成为返老药（Senolytic）。[6]

功能

p53蛋白在避免癌症发生机制上扮演重要的角色，例如，细胞凋亡 (apoptosis) 、细胞衰老（cell senescence）、基因组稳定性 (genetic stability) 、抑制血管新生 (angiogenesis)。 p53蛋白通过下列之机构达成避免癌症发生:

当DNA受损时，p53蛋白能活化DNA修复蛋白 (DNA repair proteins)。
p53蛋白能抑制细胞生长,通过使细胞周期停留于G₁/S的节律点上，以达成DNA损坏辨识。 (若能将细胞于此节律点上停留够久，DNA修复蛋白将有更充裕的时间修复DNA损坏部位，并继续细胞的生长周期。)
若细胞的DNA受损已不能修复，p53蛋白能起始细胞凋亡进程，避免拥有不正常遗传信息的细胞继续分裂生长。

活化的p53蛋白能接合于DNA，促使多个基因表现，包括基因WAF1/CIP1，其为p21蛋白之编码基因。 p21 (WAF1)接合于G₁-S/CDK (CDK2) 和S/CDK复合体 (此蛋白在G₁/S细胞周期节律点上有重要功能) 以抑制该复合体的活性。当p21蛋白 (WAF1) 与CDK2形成复合体时，细胞将无法进入到细胞分裂的阶段。而突变后的p53蛋白将可能丧失与DNA形成有效结合的能力，造成p21蛋白将无法形成，以发出停止细胞分裂的信号。因此，受损细胞将不受控制的进行细胞分裂，最终形成肿瘤。根据最近的研究，p53蛋白与RB1进程经由p14ARF蛋白相互调节的可能性更加提高。

调节

p53蛋白借由许多不同的压力形式而激发其活性，其中包括但不仅仅局限于DNA损伤 (包括 UV, IR或化学物质如过氧化氢 (hydrogen peroxide)所造成的损伤)，氧化压力 (oxidative stress)，渗透压力 (osmotic stress)，核糖核苷酸缺乏 (nucleotide depletion) 和丧失调节癌基因表现能力。这些活性激发可由两个主要的事件得出。首先，在受到压力的细胞中，p53蛋白的半衰期 (half-life) 会突然的增加，造成p53蛋白在细胞中的累积。再来则是构型变化 (conformational change) 使得p53蛋白被激发成为转录调节因子 (transcription regulator)。

参考文献

.
GRCh38: Ensembl release 89: ENSG00000141510 - Ensembl, May 2017
GRCm38: Ensembl release 89: ENSMUSG00000059552 - Ensembl, May 2017
. National Center for Biotechnology Information, U.S. National Library of Medicine.
. National Center for Biotechnology Information, U.S. National Library of Medicine.
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

This article is issued from Wikipedia. The text is licensed under Creative Commons - Attribution - Sharealike. Additional terms may apply for the media files.

[1] .

[refGRCh38Ensembl-2] GRCh38: Ensembl release 89: ENSG00000141510 - Ensembl, May 2017

[refGRCm38Ensembl-3] GRCm38: Ensembl release 89: ENSMUSG00000059552 - Ensembl, May 2017

[4] . National Center for Biotechnology Information, U.S. National Library of Medicine.

[5] . National Center for Biotechnology Information, U.S. National Library of Medicine.

[pmid28340339-6] 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.