Note to users. If you're seeing this message, it means that your browser cannot find this page's style/presentation instructions -- or possibly that you are using a browser that does not support current Web standards. Find out more about why this message is appearing, and what you can do to make your experience of our site the best it can be.

Originally published in Science Express on 11 June 2009
Science 3 July 2009:
Vol. 325. no. 5936, pp. 100 - 104
DOI: 10.1126/science.1168974
Prev | Table of Contents | Next

Reports

LXR Regulates Cholesterol Uptake Through Idol-Dependent Ubiquitination of the LDL Receptor

Noam Zelcer,* Cynthia Hong, Rima Boyadjian, Peter Tontonoz{dagger}

Cellular cholesterol levels reflect a balance between uptake, efflux, and endogenous synthesis. Here we show that the sterol-responsive nuclear liver X receptor (LXR) helps maintain cholesterol homeostasis, not only through promotion of cholesterol efflux but also through suppression of low-density lipoprotein (LDL) uptake. LXR inhibits the LDL receptor (LDLR) pathway through transcriptional induction of Idol (inducible degrader of the LDLR), an E3 ubiquitin ligase that triggers ubiquitination of the LDLR on its cytoplasmic domain, thereby targeting it for degradation. LXR ligand reduces, whereas LXR knockout increases, LDLR protein levels in vivo in a tissue-selective manner. Idol knockdown in hepatocytes increases LDLR protein levels and promotes LDL uptake. Conversely, adenovirus-mediated expression of Idol in mouse liver promotes LDLR degradation and elevates plasma LDL levels. The LXR-Idol-LDLR axis defines a complementary pathway to sterol response element–binding proteins for sterol regulation of cholesterol uptake.

Howard Hughes Medical Institute and Department of Pathology and Laboratory Medicine, University of California, Los Angeles (UCLA), Los Angeles, CA 90095, USA.

* Present address: Division of Biopharmaceutics, Leiden/Amsterdam Center for Drug Research, Gorlaeus Laboratories, Leiden University, P.O. Box 9502, 2300RA Leiden, Netherlands.

{dagger} To whom correspondence should be addressed. E-mail: ptontonoz{at}mednet.ucla.edu

Read the Full Text


THIS ARTICLE HAS BEEN CITED BY OTHER ARTICLES:
Cholesterol Worships a New Idol.
I. G. Schulman (2009)
J Mol Cell Biol 1, 75-76
   Abstract »    Full Text »    PDF »


To Advertise     Find Products

Science. ISSN 0036-8075 (print), 1095-9203 (online)