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Medientyp:
E-Artikel
Titel:
LXR Regulates Cholesterol Uptake Through Idol-Dependent Ubiquitination of the LDL Receptor
Beteiligte:
Zelcer, Noam;
Hong, Cynthia;
Boyadjian, Rima;
Tontonoz, Peter
Erschienen:
American Association for the Advancement of Science (AAAS), 2009
Erschienen in:
Science, 325 (2009) 5936, Seite 100-104
Sprache:
Englisch
DOI:
10.1126/science.1168974
ISSN:
0036-8075;
1095-9203
Entstehung:
Anmerkungen:
Beschreibung:
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.