Sci. Signal., 7 July 2009
Cholesterol Regulation Idolizing Cholesterol Control
Paula A. Kiberstis
Science, AAAS, Washington, DC 20005, USA.
The low density lipoprotein (LDL) receptor 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 LDL receptor 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 LDL receptor at the level of protein degradation. Zelcer et al. show that a sterol-responsive transcription factor called LXR induces the expression of Idol (for inducible degrader of the LDL receptor), 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.
Citation: P. A. Kiberstis, Idolizing Cholesterol Control. Sci. Signal. 2, ec232 (2009).
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