P53 |
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![](//upload.wikimedia.org/wikipedia/commons/thumb/b/bb/P53.png/250px-P53.png) |
已知的結構 |
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PDB | 直系同源搜索: PDBe RCSB |
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PDBID列表 |
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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 |
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識別號 |
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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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相關疾病 |
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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[1] |
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基因位置(小鼠) |
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![小鼠11号染色体](//upload.wikimedia.org/wikipedia/commons/thumb/a/a5/Ideogram_house_mouse_chromosome_11.svg/260px-Ideogram_house_mouse_chromosome_11.svg.png) | 染色体 | 小鼠11号染色体[3] |
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| 基因座 | 11 B3|11 42.83 cM | 起始 | 69,471,185 bp[3] |
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终止 | 69,482,699 bp[3] |
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RNA表达模式 |
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![](//upload.wikimedia.org/wikipedia/commons/thumb/3/39/PBB_GE_TP53_201746_at_fs.png/250px-PBB_GE_TP53_201746_at_fs.png)
![](//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 |
基因本體 |
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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
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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
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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
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Sources:Amigo / QuickGO |
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直系同源 |
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物種 | 人類 | 小鼠 |
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Entrez | | |
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Ensembl | | |
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UniProt | | |
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mRNA序列 | NM_001276761 NM_000546 NM_001126112 NM_001126113 NM_001126114
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NM_001126115 NM_001126116 NM_001126117 NM_001126118 NM_001276695 NM_001276696 NM_001276697 NM_001276698 NM_001276699 NM_001276760 |
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蛋白序列 | NP_000537 NP_001119584 NP_001119585 NP_001119586 NP_001119587
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NP_001119588 NP_001119589 NP_001119590 NP_001263624 NP_001263625 NP_001263626 NP_001263627 NP_001263628 NP_001263689 NP_001263690 |
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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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維基數據 |
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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
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
- ^ 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