LXR Regulates Cholesterol Uptake Through Idol-Dependent Ubiquitination of the LDL Receptor
Top Cited Papers
- 3 July 2009
- journal article
- other
- Published by American Association for the Advancement of Science (AAAS) in Science
- Vol. 325 (5936) , 100-104
- https://doi.org/10.1126/science.1168974
Abstract
Idolizing Cholesterol Control: The low-density lipoprotein receptor (LDLR) removes LDL, the so-called “bad” cholesterol particles, from the blood through a mechanism that involves LDL binding and internalization into liver cells. Because the LDLR plays a pivotal role in heart disease risk, there is substantial interest in understanding how its expression is regulated, and a large body of previous work has established the importance of transcriptional control. A new study identifies a signaling pathway that appears to regulate the LDLR at the level of protein degradation. Zelcer et al. (p. 100 , published online 11 June) show that a sterol-responsive transcription factor called LXR induces the expression of Idol (for inducible degrader of the LDLR), a protein that triggers ubiquitination of the receptor and targets it for degradation. Activation of this pathway suppresses cellular uptake of LDL and, in a mouse model, leads to higher plasma LDL levels, raising the possibility that the pathway could be targeted pharmacologically to control plasma cholesterol levels.Keywords
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