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
标识符
代号	TP53
扩展标识	OMIM：191170；MGI：98834；HomoloGene：460；GeneCards：TP53；OMA：TP53 - orthologs
基因位置（人类） 染色体 17號染色體 基因座 17p13.1 起始 7,661,779 bp 终止 7,687,538 bp
基因位置（小鼠） 染色体 小鼠11号染色体 基因座 11 B3|11 42.83 cM 起始 69,471,185 bp 终止 69,482,699 bp
RNA表达模式 Bgee 人类 小鼠（直系同源） Top expressed in ventricular zone ganglionic eminence tendon of biceps brachii stromal cell of endometrium skin of abdomen skin of leg Top expressed in tail of embryo ventricular zone 查阅更多表达数据 BioGPS 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 来源：Amigo / QuickGO
直系同源 物種 人類 小鼠 Entrez 7157 22059 Ensembl ENSG00000141510 ENSMUSG00000059552 UniProt P04637 P02340 mRNA序列 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 蛋白序列 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 基因位置 Chr 17：7.66 – 7.69 Mb Chr 11：69.47 – 69.48 Mb PubMed查询
维基数据
檢視/編輯人類 檢視/編輯小鼠

p53或p53蛋白、肿瘤蛋白p53（tumor protein p53）化学式为：C₁₉₁₁H₃₀₀₆O₅₉₂N₅₄₈S₂₂(包含甲基化)，是一种调节性转录因子和肿瘤抑制因子，在细胞应激反应时被激活，通过修复或清除受损细胞，从而防止细胞发生癌变。p53蛋白在脊椎动物中具有重要功能，其通过预防基因组突变来维持稳定性、抑制肿瘤形成 ，因此p53被称为“基因组守护者”。TP53基因是位于人类染色体17p13.1上的一种抑癌基因，其编码p53蛋白。

p53是一系列同源异构蛋白的统称，属于一种腫瘤抑制蛋白，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，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）。

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)。

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

• 肿瘤抑制基因