Feedback regulation of cholesterol uptake by the LXR–IDOL–LDLR axis

L Zhang, K Reue, LG Fong, SG Young… - … , and vascular biology, 2012 - Am Heart Assoc
L Zhang, K Reue, LG Fong, SG Young, P Tontonoz
Arteriosclerosis, thrombosis, and vascular biology, 2012Am Heart Assoc
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 …
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.
Am Heart Assoc