The role of human ADA2a in the regulation of p53 acetylation and stability

查看全文 作　　者：HUANG [1]Jing;ZHANG [1]Li;XIAO [1]Lin;XU [1]LanJun;HU [1]FanLei;SHAO [1]WenWei;LIU [1]Wei;MO [1]XiaoNing;SHI [1,2]TaiPing;QIU [1]XiaoYan

机构地区：[1]Laboratory of Medical Immunology, School of Basic Medical Science, Peking University Health Science Center, Beijing 100191, China;[2]Chinese National Human Genome Center, Beijing 100176, China

出　　处：《Chinese Science Bulletin》索引2011年第56卷第4期,共9页

基　　金：supported by the Ministry of Science and Technology for Drug Development (2009ZX09503-004);the National Natural Sciences Foundation of China (30901303);Foundation for New Youth Scholars of Peking University Health Science Center (BMU20090459) 摘　　要：The tumor suppressor protein p53 is a well-known transcription factor that functions as a critical component of the genotoxic stress response via regulating the expression of effector proteins that control cellular fate following DNA damage. The human p300/CBP-associated factor(PCAF)-containing histone acetyltransferase(HAT) complex is important for the stability and activity of p53 via its acetylation. The human homolog of yeast alteration/deficiency in activation 2a(ADA2a) is a stable component of the human PCAF-containing HAT complex. In this study,we demonstrated that p53 and hADA2a physically interact with each other in human HEK 293T cells. Using overexpression and small interfering RNA-mediated knockdown,we demonstrated that hADA2a stabilizes p53 via promoting its acetylation at lysine 320 - a PCAF-dependent acetylation site. Furthermore,hADA2a can potentiate the transcriptional activity of p53 at the BAX and p21 promoters to induce cell apoptosis and cell cycle arrest. Overall,our results establish that hADA2a,a component of the PCAF-containing histone acetyltransferase co-activator complex,is a mediator of acetylation-dependent stabilization and activation of p53 in mammalian cells. 关键词：P53基因乙酰化稳定人类调节作用组蛋白乙酰转移酶细胞周期阻滞转录因子

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The role of human ADA2a in the regulation of p53 acetylation and stability

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