Sterol regulatory element-binding transcription factor 2 (SREBF2)

Sterol regulatory element-binding transcription factor 2 (SREBF2, also known as SREBP-2) is a transcription factor belonging to the basic helix-loop-helix-leucine zipper (bHLH-Zip) family and is encoded by the SREBF2 gene located on chromosome 22. SREBP-2 is synthesized as an inactive precursor bound to the endoplasmic reticulum membrane. Upon sensing low intracellular cholesterol, the precursor undergoes proteolytic cleavage in the Golgi apparatus, releasing its N-terminal segment, which translocates to the nucleus where it binds to sterol regulatory element (SRE) sequences in the promoters of cholesterol biosynthesis and uptake genes, including those encoding the LDL receptor and HMG-CoA reductase. SREBP-2 is a central regulator of cholesterol homeostasis and plays important roles in lipid metabolism, cardiovascular disease, and cancer progression. Its activity and some genetic variants have been linked to human diseases such as hypercholesterolemia, atherosclerosis, and certain cancers.

Other names

Sterol regulatory element-binding protein 2SREBP-2SREBF2

Drugs such as statins reduce intracellular cholesterol, which leads to activation/cleavage of SREBP-2 and increased expression of LDL receptor and cholesterol biosynthetic enzymes, thus contributing to cholesterol lowering. The canonical mechanism involves regulated intramembrane proteolysis, releasing SREBP-2’s N-terminal domain to the nucleus for gene activation.