NR1H2 & NR1H3 regulate gene expression to limit cholesterol uptake

Stable Identifier
Homo sapiens
LXRs regulate gene expression to limit cholesterol uptake
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Liver X receptors NR1H3 (LXR alpha) and NR1H2 (LXR beta) are sterol-responsive transcription factors that become activated upon the engagement with their cognate oxysterol ligands. Ligand-activated NR1H2 & NR1H3 induce a genetic program aimed at reducing the cellular sterol load by limiting cholesterol uptake, attenuating cholesterol biosynthesis and promoting cholesterol efflux. This Reactome module describes the NR1H2 & NR1H3-regulated expression of MYLIP (IDOL) gene, an E3 ubiquitin ligase, that triggers ubiquitination of the low-density lipoprotein receptor (LDLR) on its cytoplasmic domain, targeting it for degradation and thereby limiting cholesterol uptake (Zelcer N et al. 2009; 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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