Sterol regulatory element-binding protein cleavage-activating protein–Sterol regulatory element-binding protein 1 protein-protein interaction (SCAP–SREBP1 interaction)

The SCAP–SREBP1 protein-protein interaction is a critical event in the regulation of lipid and cholesterol synthesis in mammalian cells. SCAP (SREBP cleavage-activating protein) is an endoplasmic reticulum (ER) sterol-sensing chaperone that binds SREBP1 (Sterol regulatory element-binding protein 1), a membrane-bound transcription factor. In low sterol conditions, SCAP escorts SREBP1 from the ER to the Golgi by incorporating the complex into COPII-coated vesicles. In the Golgi, SREBP1 undergoes sequential cleavage by proteases S1P and S2P, releasing its N-terminal portion, which enters the nucleus to activate genes involved in cholesterol and fatty acid biosynthesis. This interaction is tightly regulated by the cellular sterol status, and dysregulation contributes to diseases such as atherosclerosis, obesity, and NAFLD. Disrupting SCAP–SREBP1 binding is viewed as a potential therapeutic strategy for metabolic diseases.

Other names

SCAP–SREBP1 complex interactionSCAP–SREBP (Sterol regulatory element-binding protein) interactionSREBP cleavage-activating protein–SREBP1 binding

Inhibition of SCAP–SREBP1 interaction blocks SREBP1 transport from the endoplasmic reticulum to the Golgi, thus preventing downstream proteolytic activation of SREBP1 and nucleus entry, suppressing lipogenesis and cholesterol biosynthesis. Interfering with the SCAP–SREBP1 complex prevents transcription of lipid metabolism genes.