组蛋白甲基转移酶EZH2抑制p53活性  

Histone Methyltransferase EZH2 Inhibits p53 Activity

作　　者：胡松林[1] 贺轶博 赵亚丽[1] 雷鸣[1] 杨芬[1] 

机构地区：[1]中国航天员科研训练中心,航天医学基础与应用国家重点实验室,北京100094

出　　处：《航天医学与医学工程》2013年第6期433-436,共4页Space Medicine & Medical Engineering

基　　金：中国航天医学工程预先研究项目(2010SY5403002);航天医学基础与应用国家重点实验室研究基金资助项目(SMFA12B04;SMFA12ZC2);国家自然科学基金项目(30771104;30671076)

摘　　要：目的探讨组蛋白甲基转移酶主要成员及新的癌基因EZH2与肿瘤发生的关键分子p53之间的相互作用关系。方法利用肿瘤细胞系U2OS细胞,首先以免疫共沉淀方法进行了EZH2与p53的相互作用研究,进而采用蛋白质印迹及实时定量PCR方法对p53靶基因的表达进行了分析,最后利用流式细胞术及细胞核染色法分析了EZH2对细胞周期的影响。结果 p53与EZH2具有相互作用,EZH2抑制p53下游靶基因p21、mdm2及puma的表达;流式细胞术提示EZH2抑制p53诱发的细胞周期阻滞,进而支持了EZH2能再抑制p53的活性。结论本研究首次发现EZH2对p53转录活性及其生物学功能的抑制作用,丰富了p53调控网络,提出了EZH2参与肿瘤发生发展的新的分子机制,为肿瘤防治提供了新的研究线索。Objective It is to explore the unknown relationship of interaction between EZH2 and p53. EZH2, as a major component of histone methyhransferase family and a novel oncogene, is positively linked with tumor oc- currence and its invasive capacity, p53 is a key molecule in tumorgenesis. Methods In the tumor celline U2OS, co-immunoprecipitation was employed to explore the interaction of EZH2 and p53, Western blotting and real time PCR methods were used to analyse the expression of p53 target genes. Finally, cell-sorting technique and nuclear staining were used to analyse the effects of EZH2 on cell cycle progression. Results There existed the protein interaction of EZH2 and p53. In further experiments, EZH2 inhibited the expression of the down- stream target genes of p53 including p21, mdm2 and puma. In addition, it was showed with cell-sorting tech- nique that p53-induced cell cycle arrest was inhibited by EZH2, further supporting that EZH2 could repress the p53 activity. Conclusion The present study first reveals that EZH2 suppresses p53 transcriptional activity and its biological function, enriches the regulatory network of p53 and offers a novel molecular mechanism in onco- genesis. It is also to provide a new evdience for studying tumor prevention and therapy.

关 键 词：P53 EZH2 P21 肿瘤 组蛋白甲基化 

分 类 号：R854[医药卫生—航空、航天与航海医学]