Cholesterol Regulation

Idolizing Cholesterol Control

Science Signaling  07 Jul 2009:
Vol. 2, Issue 78, pp. ec232
DOI: 10.1126/scisignal.278ec232

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.

N. Zelcer, C. Hong, R. Boyadjian, P. Tontonoz, LXR regulates cholesterol uptake through idol-dependent ubiquitination of the LDL receptor. Science 325, 100–104 (2009). [Abstract] [Full Text]