Wei L N, Farooqui M, Hu X
Department of Pharmacology, University of Minnesota Medical School, Minneapolis, Minnesota 55455, USA.
J Biol Chem. 2001 May 11;276(19):16107-12. doi: 10.1074/jbc.M010185200. Epub 2001 Mar 5.
Receptor-interacting protein 140 (RIP140) interacts with retinoic acid receptor and retinoid X receptor in a ligand-dependent manner and suppresses retinoic acid (RA) induction of its target genes. The receptor-interacting motif is mapped to a C-terminal peptide sequence (LTKTNPILYYMLQK) of RIP140. The functional role of this motif in mediating the suppressive effects of RIP140 on RA induction is demonstrated in mutation studies. RA induces coimmunoprecipitation of histone deacetylase 3 with retinoic acid receptor/retinoid X receptor in the presence of wild type RIP140, but not in the presence of the C-terminal motif-deleted RIP140. A decrease in histone acetylation on the promoter region that carries a RA response element is associated with the expression of wild type RIP140, but not with expression of the mutant RIP140, in a dose-dependent manner. These data provide a molecular explanation for RIP140 acting as a novel ligand-dependent, negative modulator of RA-regulated gene expression.
受体相互作用蛋白140（RIP140）以配体依赖的方式与视黄酸受体和类视黄醇X受体相互作用，并抑制视黄酸（RA）对其靶基因的诱导作用。受体相互作用基序定位于RIP140的C末端肽序列（LTKTNPILYYMLQK）。突变研究证明了该基序在介导RIP140对RA诱导的抑制作用中的功能作用。在野生型RIP140存在的情况下，RA可诱导组蛋白去乙酰化酶3与视黄酸受体/类视黄醇X受体的共免疫沉淀，但在C末端基序缺失的RIP140存在时则不会。携带RA反应元件的启动子区域上组蛋白乙酰化的减少与野生型RIP140的表达呈剂量依赖性相关，但与突变型RIP140的表达无关。这些数据为RIP140作为RA调节基因表达的新型配体依赖负调节剂提供了分子解释。
