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Gp78, a Membrane-Anchored Ubiquitin Ligase, Associates with Insig-1 and Couples Sterol-Regulated Ubiquitination to Degradation of HMG CoA Reductase

Song, Bao-Liang, Sever, Navdar, DeBose-Boyd, Russell A.·2005·Molecular Cell
DOI 10.1016/j.molcel.2005.08.009
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Abstract

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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Research works printed but not linked: 36

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Metadata

Authors
Song, B.-L., Sever, N., & DeBose-Boyd, R. A.
Venue
Molecular Cell
Publisher
Elsevier BV
Published
2005-09
Volume
19
Issue
6
Pages
829-840
ISSN
1097-2765
DOI
10.1016/j.molcel.2005.08.009
Cited by
328
References
3
Language
en
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