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Arterioscler Thromb Vasc Biol. 2012 Nov;32(11):2541-6. doi: 10.1161/ATVBAHA.112.250571. Epub 2012 Aug 30.

Feedback regulation of cholesterol uptake by the LXR-IDOL-LDLR axis.

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1
Howard Hughes Medical Institute, UCLA School of Medicine, Box 951662, Los Angeles, CA 90095-1662, USA.

Abstract

Inducible degrader of the low-density lipoprotein receptor (IDOL) is an E3 ubiquitin ligase that mediates the ubiquitination and degradation of the low-density lipoprotein receptor (LDLR). IDOL expression is controlled at the transcriptional level by the cholesterol-sensing nuclear receptor liver X receptor (LXR). In response to rising cellular sterol levels, activated LXR induces IDOL production, thereby limiting further uptake of exogenous cholesterol through the LDLR pathway. The LXR-IDOL-LDLR mechanism for feedback inhibition of cholesterol uptake is independent of and complementary to the sterol regulatory element-binding protein pathway. Since the initial description of the LXR-IDOL pathway, biochemical studies have helped to define the structural basis for both IDOL target recognition and LDLR ubiquitin transfer. Recent work has also suggested links between IDOL and human lipid metabolism.

PMID:
22936343
PMCID:
PMC4280256
DOI:
10.1161/ATVBAHA.112.250571
[Indexed for MEDLINE]
Free PMC Article
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