辅抑制子SMRT特异地抑制孤儿核受体hB1F/hLRH-1的转录活性(英文)  

Corepressor SMRT Specifically Represses the Transcriptional Activity of Orphan Nuclear Receptor hB1F/hLRH-1

作　　者：徐平龙[1] 孔玉英[1] 谢幼华[1] 汪垣[1] 

机构地区：[1]中国科学院上海生命科学研究院生物化学与细胞生物学研究所分子生物学国家重点实验室,上海200031

出　　处：《生物化学与生物物理学报》2003年第10期897-903,共7页

基　　金：国家自然科学基金 (No .30 1 0 0 0 88);国家高技术研究与发展计划 ( 863计划 ) (No .2 0 0 1AA2 2 1 2 61 );科技部基础研究计划 (No .G1 9990 5 4 1 0 5 );上海科委启明星 (No .0 1QA1 40 4 6)项目资助~~

摘　　要：孤儿核受体hB1F (NR5A2 ,也称之为LRH 1、FTF或CPF)在胆汁酸合成代谢相关基因、乙型肝炎病毒基因和一些肝特异性基因的表达调控中起着非常重要的作用。为了认识hB1F转录激活的分子机制 ,对核受体辅抑制子SMRT在其中的作用进行了研究。利用与GAL4 DBD融合的hB1F所进行的报告基因分析发现 ,SMRT能够以剂量依赖的方式显著地抑制hB1F的反式激活能力 ,但对融合蛋白质的表达没有影响。而且 ,SMRT也能够明显地抑制hB1F响应的乙肝病毒增强子II 核心启动子的活性 ,对增强子II的点突变分析表明这种抑制作用主要是由hB1F介导的。共转染实验显示 ,SMRT在多种细胞中都表现出抑制作用。有意思的是 ,哺乳动物细胞的双杂交与体外的GST下拉 (pull down)分析都表明hB1F与SMRT之间不存在直接的相互作用。实验数据首次证实 ,辅抑制子SMRT可能通过间接的方式特异地抑制孤儿核受体hB1F的转录活性。The orphan nuclear receptor hB1F (also known as NR5A2, LRH-1, FTF or CPF) plays important roles in regulating the expression of several cellular and viral genes actively involved in a wide range of biological processes such as the bile acid biosynthesis, liver specific gene regulatory network and hepatitis B virus replication. The activity of nuclear receptors is regulated by multiple mechanisms, including coactivation and corepression. In this study, it was found that the silencing mediator for retinoic acid receptor and thyroid hormone receptor (SMRT) specifically represses the transcriptional activity of hB1F, on either GAL4 dependent reporter system or the hB1F-responsive HBV enhancer II/core promoter. The repression imposed by SMRT is observed in different cell lines. Interestingly, hB1F couldn’t interact with SMRT directly, as demonstrated by mammalian two-hybrid analysis or GST pull-down assay. Taken together, it can be concluded for the first time that the transcriptional activity of hB1F is regulated specifically by the corepressor SMRT via an indirect mechanism.

关 键 词：孤儿核受体 抑制 乙肝病毒增强子II 核心启动子 SMRT 表达调控 

分 类 号：R346[医药卫生—基础医学]