NR1H2,3 binds the MYLIP gene

Stable Identifier
R-HSA-9623366
Type
Reaction [binding]
Species
Homo sapiens
Compartment
Synonyms
LXR binds IDOL gene
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Myosin regulatory light chain interacting protein (MYLIP, aka inducible degrader of the LDLR (IDOL)) is a transcriptional target of the cholesterol-sensing liver X receptors (LXRs, NR1H2 and NR1H3) (Zelcer N et al. 2009, Hong C et al. 2010, Sorrentino V & Zelcer N 2012, Zhang L et al. 2012). LXR agonists induced MYLIP expression in multiple cells in an LXR-dependent manner, including human liver carcinoma HepG2 cells, primary mouse hepatocytes and macrophages (Zelcer N et al. 2009). NR1H2, NR1H3 activate target genes by binding to consensus elements (LXREs) in their promoters. Electrophoretic mobility shift assays coupled with site-directed mutagenesis showed that mouse Mylip (Idol) gene induction occured through binding of the LXR:RXR heterodimer to a functional LXR response element (LXRE) which was identified approximately 2.5 kb upstream of the mouse Mylip (Idol) translation start site (Zelcer et al. 2009). MYLIP (IDOL) functions as an E3 ubiquitin-protein ligase to promote ubiquitylation and lysosomal degradation of the low density lipoprotein receptor (LDLR) (Zelcer N et al. 2009; Zhang et al. 2012; Scotti E et al. 2011; Sorrentino V et al. 2013 a,b). NR1H2 or NR1H3 can increase MYLIP expression, which in turn triggers ubiquitination of the LDLR on its cytoplasmic domain, thereby targeting it for degradation (Zelcer N et al. 2009, Sorrentino V & Zelcer N 2012, Zhang L et al. 2012).

Literature References
PubMed ID Title Journal Year
22936343 Feedback regulation of cholesterol uptake by the LXR-IDOL-LDLR axis

Zhang, L, Reue, K, Fong, LG, Young, SG, Tontonoz, P

Arterioscler. Thromb. Vasc. Biol. 2012
19520913 LXR regulates cholesterol uptake through Idol-dependent ubiquitination of the LDL receptor

Zelcer, N, Hong, C, Boyadjian, R, Tontonoz, P

Science 2009
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