期刊
CELL METABOLISM
卷 1, 期 6, 页码 379-391出版社
CELL PRESS
DOI: 10.1016/j.cmet.2005.04.010
关键词
-
资金
- NIA NIH HHS [R01 AG011085] Funding Source: Medline
The sterol regulatory element binding protein (SREBP) family of transcription factors controls cholesterol and lipid metabolism. The nuclear forms of these proteins are rapidly degraded by the ubiquitin-proteasome pathway, but the signals and factors required for this are unknown. Here, we identify a phosphodegron in SREBP1a that serves as a recognition motif for the SCFFbw7 ubiquitin ligase. Fbw7 interacts with nuclear SREBP1a and enhances its ubiquitination and degradation in a manner dependent on the phosphorylation of T426 and S430 by GSK-3. Fbw7 also degrades nuclear SREBP1c and SREBP2, and inactivation of endogenous Fbw7 results in stabilization of nuclear SREBP1 and -2, enhanced expression of SREBP target genes, enhanced synthesis of cholesterol and fatty acids, and enhanced receptor-mediated uptake of LDL. Thus, our results suggest that Fbw7 may be a major regulator of lipid metabolism through control of the phosphorylation-dependent degradation of the SREBP family of transcription factors.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据