SREBPs: Transcriptional Mediators of Lipid Homeostasis

Sterol regulatory element-binding proteins (SREBPs)are a family of membrane-bound transcription factorsthat regulate cellular lipid synthesis and the clearance ofatherogenic lipoproteins from the blood. They were initially isolated as proteins that transcriptionally regulatedtwo genes involved in cholesterol homeostasis, the lowdensity lipoprotein (LDL) receptor, a transmembraneprotein responsible for binding and internalizing LDLcholesterol from plasma, and 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) synthase, a key enzymein the cholesterol biosynthesis pathway (Goldstein et al.2002). Subsequent studies have revealed that SREBPs directly activate the expression of more than 30 genes dedicated to the synthesis and uptake of cholesterol, fattyacids, triglycerides, and phospholipids, as well as theNADPH cofactor required to synthesize these molecules(Horton et al. 2002). In this paper, we will focus on thetranscriptional activating properties of each SREBP family member, and how the regulation of each SREBP isoform provides a mechanism for cells to coordinately andindependently regulate the lipid biosynthetic pathways...