NHERF1 and NHERF2 regulation of SR-B1 stability via ubiquitination and proteasome degradation
NHERF1 and NHERF2 regulation of SR-B1 stability via ubiquitination and proteasome degradation
复制标题
NHERF1 和 NHERF2 通过泛素化和蛋白酶体降解调节 SR-B1 稳定性
DOI：
10.1016/j.bbrc.2017.06.175
复制
发表时间：
2017-09-02
影响因子：
3.1
通讯作者：
Hu, Zhigang
中科院分区：
文献类型：
--
作者：
Lu, Xiao;He, Lingfeng;Hu, Zhigang
清道夫受体B类1型（SR-B1），HDL受体在肝脏、类固醇生成组织和血管细胞（包括巨噬细胞）中的胆固醇代谢中起关键作用。SR-B1在转录、转录后和翻译后水平受到调控。我们以前提供的证据表明，PDZ结构域含有NHERF 1和NHERF 2调节SR-B1蛋白水平转录后，虽然NHERF 1和NHERF 2调节SR-B1蛋白水平的潜在机制还没有很好地理解。在这项研究中，我们证明了SR-B1是通过泛素-蛋白酶体途径在细胞内降解的，并且SR-B1可以在1（500）和K508残基处被泛素化。NHERF 1或NHERF 2的过表达增强了SR-B1的泛素化和降解。NHERF 1和NHERF 2分别促进位点K508和K500处的SR-B1遍在蛋白化。这些结果表明，NHERF 1和NHERF 2下调SR-B1至少部分通过泛素/蛋白酶体途径。(C)2017爱思唯尔公司All rights reserved.
Scavenger receptor class B type 1 (SR-B1), an HDL receptor plays a crucial role in cholesterol metabolism in the liver, steroidogenic tissues, and vascular cells including macrophages. SR-B1 is subject to regulation at the transcription, posttranscription and posttranslational levels. We previously provided evidence that PDZ domain containing NHERF1 and NHERF2 regulate SR-B1 protein levels post transcriptionally, although the underlying mechanism(s) by which NHERF1 and NHERF2 regulate SR-B1 protein levels is not well understood. In this study, we demonstrate that SR-B1 is degraded intracellularly via ubiquitin-proteasome pathway and that SR-B1 can be ubiquitinated at 1(500 and K508 residues. Overexpression of NHERF1 or NHERF2 enhanced SR-B1 ubiquitination and degradation. NHERF1 and NHERF2 promote SR-B1 ubiquitination at sites K508 and K500, respectively. These results suggest that NHERF1 and NHERF2 down-regulated SR-B1 at least in part via the ubiquitin/proteasome pathway. (C) 2017 Elsevier Inc. All rights reserved.