title: Feedback regulation of cholesterol uptake by the LXR-IDOL-LDLR axis.
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.
authors.affiliation: Howard Hughes Medical Institute, UCLA School of Medicine, Box 951662, Los Angeles, CA 90095-1662, USA.
authors.forename: Li
authors.initials: L
authors.lastname: Zhang
authors.forename: Karen
authors.initials: K
authors.lastname: Reue
authors.forename: Loren G
authors.initials: LG
authors.lastname: Fong
authors.forename: Stephen G
authors.initials: SG
authors.lastname: Young
authors.forename: Peter
authors.initials: P
authors.lastname: Tontonoz
mesh_terms: D000818:Animals; D050197:Atherosclerosis / Q000097:blood / Q000201:enzymology* / Q000235:genetics; D001692:Biological Transport; D002784:Cholesterol / Q000097:blood / Q000378:metabolism*; D025461:Feedback, Physiological; D015971:Gene Expression Regulation, Enzymologic; D006801:Humans; D008099:Liver / Q000201:enzymology*; D000071518:Liver X Receptors; D057093:Orphan Nuclear Receptors / Q000378:metabolism*; D011973:Receptors, LDL / Q000378:metabolism*; D013379:Substrate Specificity; D044767:Ubiquitin-Protein Ligases / Q000235:genetics / Q000378:metabolism*; D054875:Ubiquitination
chemical_list: D000071518:Liver X Receptors; D057093:Orphan Nuclear Receptors; D011973:Receptors, LDL; D002784:Cholesterol; C403126:MYLIP protein, human; D044767:Ubiquitin-Protein Ligases