Figure 3: Regulation of cholesterol homeostasis via SREBP and HMG-CoA reductase. When the cholesterol (C) or oxysterol level is high, they can bind to sterol sensing domain (SSD) of the sterol regulatory element binding protein (SREBP) cleavage activating protein (SCAP) or HMG-CoA reductase. In this case, SREBP will be stabilized on ER to be inactivated, and HMG-CoA reductase will be degraded therefore cholesterol synthesis will be inhibited. The low cholesterol level causes release of Insig and allows the SCAP/SREBP to enter the COPII coated vesicle. The vesicle will move to Golgi and the SREBP will be cleaved into the activated form. The mature SREBPs enter into nucleus to bind to sterol regulatory elements (SREs) to induce the downstream genes expression.