泛素连接酶
生物
还原酶
内质网相关蛋白降解
泛素
甾醇
HMG-CoA还原酶
生物化学
甾醇调节元件结合蛋白
细胞生物学
泛素蛋白连接酶类
7-脱氢胆固醇还原酶
酶
胆固醇
基因
作者
Bao-Liang Song,Navdar Sever,Russell A. DeBose‐Boyd
出处
期刊:Molecular Cell
[Elsevier]
日期:2005-09-01
卷期号:19 (6): 829-840
被引量:332
标识
DOI:10.1016/j.molcel.2005.08.009
摘要
Summary
Sterol-regulated ubiquitination is an obligatory step in ER-associated degradation (ERAD) of HMG CoA reductase, a rate-limiting enzyme in cholesterol synthesis. Accelerated degradation of reductase, one of several strategies animal cells use to limit production of cholesterol, requires sterol-induced binding of the enzyme to ER membrane proteins called Insigs. Once formed, the reductase-Insig complex is recognized by a putative membrane-associated ubiquitin ligase (E3) that mediates the reductase ubiquitination reaction. Here, we show that gp78, a membrane bound E3, binds to Insig-1 and is required for sterol-regulated ubiquitination of reductase. In addition, gp78 couples regulated ubiquitination to degradation of reductase by binding to VCP, an ATPase that plays a key role in recognition and degradation of ERAD substrates. The current results identify gp78 as the E3 that initiates sterol-accelerated degradation of reductase, and Insig-1 as a bridge between gp78/VCP and the reductase substrate.
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