Title :
LXR regulates cholesterol uptake through
Idol-dependent ubiquitination of the
LDL receptor
Abstract :
- Cellular cholesterol levels reflect a balance between uptake, efflux, and endogenous synthesis
- Here we show that the sterol-responsive nuclear liver X receptor ( LXR ) helps maintain cholesterol homeostasis, not only through promotion of cholesterol efflux but also through suppression of low-density lipoprotein ( LDL ) uptake
- LXR inhibits the LDL receptor ( LDLR ) pathway through transcriptional induction of Idol ( inducible degrader of the LDLR ), an E3 ubiquitin ligase that triggers ubiquitination of the LDLR on its cytoplasmic domain , thereby targeting it for degradation
- LXR ligand reduces, whereas LXR knockout increases, LDLR protein levels in vivo in a tissue-selective manner
- Idol knockdown in hepatocytes increases LDLR protein levels and promotes LDL uptake
- Conversely, adenovirus-mediated expression of Idol in mouse liver promotes LDLR degradation and elevates plasma LDL levels
- The LXR- Idol- LDLR axis defines a complementary pathway to sterol response element-binding proteins for sterol regulation of cholesterol uptake
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