ER stress differentially regulates the stabilities of ERAD ubiquitin ligases and their substrates
ER stress differentially regulates the stabilities of ERAD ubiquitin ligases and their substrates
复制标题
ER 应激差异调节 ERAD 泛素连接酶及其底物的稳定性
DOI：
10.1016/j.bbrc.2006.11.121
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发表时间：
2007-01-26
影响因子：
3.1
通讯作者：
Fang, Shengyun
中科院分区：
文献类型：
--
作者：
Shen, Yuxian;Ballar, Petek;Fang, Shengyun
内质网（ER）应激诱导的错误折叠蛋白在ER中的积累刺激ER相关降解（ERAD）过程。ERAD反过来消除了这些错误折叠的蛋白质。泛素化酶的上调是内质网应激增强ERAD的重要机制。然而，异位过表达的泛素化酶往往不能增加，有时，抑制ERAD。为了进一步了解ER应激如何调节ERAD，我们研究了ER应激对泛素连接酶（E3）gp78介导的ERAD以及gp78和另一种ERAD E3 Hrd1的稳定性的影响。结果表明，ER应激诱导剂衣霉素显着增强ERAD的细胞，无论是表达内源性或过表达gp78。重要的是，ER应激可以增加ERAD，即使新的蛋白质合成被放线菌酮抑制。令人惊讶的是，衣霉素处理稳定gp78，建立ERAD E3和ERAD底物，以及，长达8小时。相比之下，ER应激除了降低Hrd 1的总遍在蛋白化水平外，对另一种E3 Hrd 1的稳定性几乎没有影响。我们的数据表明，ER应力差异调节ERAD E3及其底物的稳定性，这可能是一种新的机制，ER应力增加ERAD。(c)2006年由Elsevier Inc.出版
Endoplasmic reticulum (ER) stress-induced accumulation of misfolded proteins in the ER stimulates the ER-associated degradation (ERAD) process. ERAD in turn eliminates those misfolded proteins. Upregulation of ubiquitination enzymes is an essential mechanism by which ER stress enhances ERAD. However, ectopic overexpression of ubiquitination enzymes often fails to increase, and sometimes, inhibits ERAD. To further understand how ER stress regulates ERAD, we studied the effects of ER stress on ubiquitin ligase (E3) gp78-mediated ERAD and on the stabilities of gp78 and another ERAD E3 Hrd1. The results showed that ER stress-inducing agent tunica-mycin significantly enhanced ERAD in cells that either express endogenous or overexpress gp78. Importantly, ER stress could increase ERAD even when new protein synthesis was inhibited by cycloheximide. Surprisingly, tunicamycin treatment stabilized gp78, an established ERAD E3 and an ERAD substrate as well, for up to 8 h. By contrast, ER stress had little effects on the stability of another E3 Hrd1 except that it reduced the total ubiquitination level of Hrd1. Our data suggest that ER stress differentially regulates the stabilities of ERAD E3s and their substrates, which may represent a novel mechanism by which ER stress increases ERAD. (c) 2006 Published by Elsevier Inc.