P53 |
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![](//images.weserv.nl/?url=//upload.wikimedia.org/wikipedia/commons/thumb/b/bb/P53.png/250px-P53.png) |
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识别号 |
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别名 | TP53;, BCC7, LFS1, P53, TRP53, tumor protein p53, BMFS5, Genes, p53 |
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外部ID | OMIM:191170 MGI:98834 HomoloGene:460 GeneCards:TP53 |
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相关疾病 |
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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] |
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RNA表达模式 |
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![](//images.weserv.nl/?url=//upload.wikimedia.org/wikipedia/commons/thumb/3/39/PBB_GE_TP53_201746_at_fs.png/250px-PBB_GE_TP53_201746_at_fs.png)
![](//images.weserv.nl/?url=//upload.wikimedia.org/wikipedia/commons/thumb/4/4b/PBB_GE_TP53_211300_s_at_fs.png/250px-PBB_GE_TP53_211300_s_at_fs.png) |
查阅更多表达数据 |
基因本体 |
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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
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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
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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 • 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
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Sources:Amigo / QuickGO |
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直系同源 |
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物种 | 人类 | 小鼠 |
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Entrez | | |
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Ensembl | | |
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UniProt | | |
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mRNA序列 | | |
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蛋白序列 | | |
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基因位置(UCSC) | Chr 17: 7.66 – 7.69 Mb | Chr 11: 69.47 – 69.48 Mb |
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PubMed查找 | [4] | [5] |
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维基数据 |
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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。不过依据胺基酸序列进行计算后发现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程序,避免拥有不正常遗传资讯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程序经由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
- ^ 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
参见
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| (2.2) 其他的Cys4结构 | |
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| (2.3) Cys2His2 | |
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| (2.4) Cys6 | |
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| (2.5)交替composition | |
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| (3.2)配对框 | |
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| (3.6)TEA结构域 | transcriptional enhancer factor( 1、 2、 3、 4) |
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| | (4) 具有小凹槽触点的β-支架因子 |
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| (4.3) p53样转录因子 | |
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| (4.11) Runt | |
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| | (0) 其他转录因子 |
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| (0.2) HMGI(Y) | |
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| (0.6) Miscellaneous | |
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