Feedback Regulation of Cholesterol Uptake by the LXR–IDOL–LDLR Axis
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. IDOL expression is controlled at the transcriptional level by the cholesterol-sensing nuclear receptor LXR. In response to rising cellular sterol levels, activated LXR induces IDOL production, thereby limiting further uptake of exogenous cholesterol through the low-density lipoprotein receptor pathway. The LXR–IDOL–low-density lipoprotein receptor 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 low-density lipoprotein receptor ubiquitin transfer. Recent work has also suggested links between IDOL and human lipid metabolism.
- Received July 10, 2012.
- Accepted August 17, 2012.
- © 2012 American Heart Association, Inc.