Receptor-interacting protein 140 directly recruits histone deacetylases for gene silencing
Receptor-interacting protein 140 directly recruits histone deacetylases for gene silencing
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DOI：
10.1074/jbc.m004821200
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发表时间：
2000-12-29
影响因子：
4.8
通讯作者：
Farooqui, M
中科院分区：
文献类型：
--
作者：
Wei, LN;Hu, XL;Farooqui, M
受体相互作用蛋白140（RIP 140）编码组蛋白去乙酰化酶（HDAC）的激活剂敏感性抑制活性。RIP 140与HDAC 1和HDAC 3的直接相互作用发生在体外和体内，如在免疫共沉淀和谷胱甘肽S-转移酶下拉实验中所证明的。基于谷胱甘肽S-转移酶下拉实验，RIP 140的HDAC相互作用结构域被定位到其N-末端结构域，在氨基酸78和303之间。在染色质免疫沉淀试验中，它表明，组蛋白脱乙酰化发生在染色质区域的Ga 14结合位点作为结果的Ga 14 DNA结合域拴系RIP表达。来自用RIP 140和HDAC转染的细胞的RIP 140的免疫复合物能够在体外使组蛋白脱乙酰化。这项研究提出了RIP 140作为核受体作用的负共调节因子的第一个证据，通过直接招募组蛋白脱乙酰酶，并将RIP 140归类为能够直接与HDAC相互作用的新型负共调节因子。
Receptor-interacting protein 140 (RIP140) encodes a histone deacetylase (HDAC) inhibitor-sensitive repressive activity. Direct interaction of RIP140 with HDAC1 and HDAC3 occurs in vitro and in vivo as demonstrated in co-immunoprecipitation and glutathione S-transferase pull-down experiments. The HDAC-interacting domain of RIP140 is mapped to its N-terminal domain, between amino acids 78 and 303 based upon glutathione S-transferase pull-down experiments. In chromatin immunoprecipitation assays, it is demonstrated that histone deacetylation occurs at the chromatin region of the Ga14 binding sites as a result of Ga14 DNA binding domain-tethered RIP expression. The immunocomplexes of RIP140 from cells transfected with RIP140 and HDAC are able to deacetylate histone proteins in vitro. This study presents the first evidence for RIP140 as a negative coregulator for nuclear receptor actions by directly recruiting histone deacetylases and categorizes RIP140 as a novel negative coregulator that is able to directly interact with HDACs.