Figure 5.

UBXD8 (ubiquitin regulatory X domain–containing protein 8) governs cholesterol synthesis in hepatocytes. A, HepG2 control and 2 independent UBXD8KO clones were sterol-depleted by culture in β-methyl-cyclodextrin (β-MCD)–containing medium for 16 h. Subsequently, cells were labeled for 45 min with [¹⁴C]-acetate in the presence of 10 μmol/L 25-HC or 2.5 μg/mL simvastatin, as indicated. The [¹⁴C]-labeled nonsaponifiable lipid fraction, extracted from samples containing an equal amount of cell protein, was quantified by scintillation counting. Each bar and error are the mean±SD of percent HMGCR (3-hydroxy-3-methylglutaryl coenzyme A reductase) activity (n=6); *P<0.05, ***P<0.005. B, Schematic representation of the role of UBXD8 in regulating sterol-stimulated degradation of HMGCR. In the absence of UBXD8 or its UBX domain, extraction of HMGCR to the cytosol en route to proteosomal degradation is abolished.