类视黄醇配体对RIP140的影响：与类视黄醇受体的分子相互作用及生物学活性

Effects of retinoid ligands on RIP140: molecular interaction with retinoid receptors and biological activity.

作者信息

Farooqui Mariya, Franco Peter J, Thompson Jim, Kagechika Hiroyuki, Chandraratna Roshantha A S, Banaszak Len, Wei Li-Na

机构信息

Department of Pharmacology and Biochemistry, University of Minnesota Medical School, Minneapolis, Minnesota 55455, USA.

出版信息

Biochemistry. 2003 Feb 4;42(4):971-9. doi: 10.1021/bi020497k.

DOI:10.1021/bi020497k

PMID:12549917

Abstract

Receptor interacting protein 140 (RIP140) interacts with retinoic acid receptor (RAR) and retinoid X receptor (RXR) constitutively, but hormone binding enhances this interaction. The ligand-independent interaction is mediated by the amino and central regions of RIP140 which contain a total of nine copies of the LXXLL motif, whereas the agonist-induced interaction is mediated by its carboxyl terminus which contains a novel motif (1063-1076, LTKTNPILYYMLQK). The ligand-independent interaction could be enhanced slightly by agonists, whereas the ligand-dependent interaction was strictly agonist dependent for both RAR and RXR. In the context of heterodimers, ligand occupancy of RXR played a more dominant role for both molecular interaction and biological activity of RIP140. Competition and mutation studies demonstrated an essential role for (1067)Asn and (1073)Met for a ligand-dependent interaction. A model was proposed to address the constitutive and agonist-dependent interaction of RIP140 with RAR/RXR.

摘要

受体相互作用蛋白140（RIP140）可与视黄酸受体（RAR）和视黄醇X受体（RXR）持续相互作用，但激素结合会增强这种相互作用。RIP140的氨基和中央区域介导了不依赖配体的相互作用，该区域总共包含九个LXXLL基序拷贝，而激动剂诱导的相互作用则由其羧基末端介导，该末端包含一个新基序（1063 - 1076，LTKTNPILYYMLQK）。激动剂可略微增强不依赖配体的相互作用，而对于RAR和RXR，依赖配体的相互作用则严格依赖激动剂。在异二聚体的情况下，RXR的配体占据对RIP140的分子相互作用和生物学活性均发挥更主要的作用。竞争和突变研究表明，（1067）Asn和（1073）Met对于依赖配体的相互作用至关重要。提出了一个模型来解释RIP140与RAR/RXR的持续和依赖激动剂的相互作用。