Noam Zelcer1, Cynthia Hong1, Rima Boyadjian1, Peter Tontonoz1
1Howard Hughes Medical Institute and Department of Pathology and Laboratory Medicine, University of California, Los Angeles (UCLA), Los Angeles, CA 90095, USA.
Tóm tắt
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.
