P53

p53或p53蛋白、肿瘤蛋白p53（tumor protein p53），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^[6]。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^[7] ，因此p53被称为“基因组守护者”^[8]。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^[9]。

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[1]
基因位置（人类） 染色体 17號染色體[2] 基因座 17p13.1 起始 7,661,779 bp[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] 基因座 11 B3|11 42.83 cM 起始 69,471,185 bp[3] 终止 69,482,699 bp[3]
RNA表达模式
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
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​（UCSC）	Chr 17: 7.66 – 7.69 Mb	Chr 11: 69.47 – 69.48 Mb
PubMed​查找	[4]	[5]
維基數據
檢視/編輯人類 檢視/編輯小鼠

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^[10]。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^[11]，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）。^[11]

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)。