Herp enhances ER-associated protein degradation by recruiting ubiquilins
Herp enhances ER-associated protein degradation by recruiting ubiquilins
复制标题
DOI：
10.1016/j.bbrc.2008.02.086
复制
发表时间：
2008-05-02
影响因子：
3.1
通讯作者：
Yoon, Jong-Bok
中科院分区：
文献类型：
--
作者：
Kim, Tae-Yeon;Kim, Eunmin;Yoon, Jong-Bok
内质网相关蛋白降解（ERAD）是内质网的一个蛋白质质量控制系统，它通过蛋白酶体依赖性降解来消除错误折叠的蛋白质，并确保只有正确折叠的蛋白质从内质网中输出。Herp是一种通过ER应激上调的ER膜蛋白，参与ERAD的调节。在目前的研究中，我们表明，Herp与泛素家族的成员，其功能作为一个穿梭因子提供泛素化底物的蛋白酶体降解的相互作用。通过小干扰RNA敲低泛素表达使ERAD底物CD3 δ稳定，而它不改变或增加所测试的非ERAD底物的降解。CD3 δ通过过表达的Herp突变体稳定，所述Herp突变体能够结合泛素，但由于跨膜结构域的缺失而在ER膜靶向中受损。我们的数据表明，Herp结合泛素蛋白在ERAD途径中起着重要的作用，并且泛素特异性地参与降解仅一部分泛素化靶点，包括Herp依赖性ERAD底物。(C)2008年爱思唯尔公司All rights reserved.
ER-associated protein degradation (ERAD) is a protein quality control system of ER, which eliminates misfolded proteins by proteasome-dependent degradation and ensures export of only properly folded proteins from ER. Herp, an ER membrane protein upregulated by ER stress, is implicated in regulation of ERAD. In the present study, we show that Herp interacts with members of the ubiquilin family, which function as a shuttle factor to deliver ubiquitinated substrates to the proteasome for degradation. Knockdown of ubiquilin expression by small interfering RNA stabilized the ERAD substrate CD3 delta, whereas it did not alter or increased degradation of non-ERAD substrates tested. CD3 delta was stabilized by overexpressed Herp mutants which were capable of binding to ubiquilins but were impaired in ER membrane targeting by deletion of the transmembrane domain. Our data suggest that Herp binding to ubiquilin proteins plays an important role in the ERAD pathway and that ubiquilins are specifically involved in degradation of only a subset of ubiquitinated targets, including Herp-dependent ERAD substrates. (C) 2008 Elsevier Inc. All rights reserved.