Sterol regulatory element-binding protein 1 (SREBP-1) (SREBP-1)

Sterol regulatory element-binding protein 1 (SREBP-1) is a master transcriptional regulator of lipid homeostasis, specifically governing the expression of genes involved in de novo lipogenesis and fatty acid synthesis (UniProt P36956). It is synthesized as an inactive precursor tethered to the endoplasmic reticulum (ER) membrane; upon activation, it undergoes a multi-step proteolytic processing involving the SCAP protein and Site-1/Site-2 proteases to release its active N-terminal domain into the nucleus (Brown & Goldstein, Cell 1997). In metabolic diseases such as non-alcoholic fatty liver disease (NAFLD) and type 2 diabetes, SREBP-1 is often overactivated, leading to excessive fat accumulation in the liver and insulin resistance (Horton et al., J Clin Invest 2002). Furthermore, many cancers upregulate the SREBP-1 pathway to meet the high demand for lipids required for rapid cell membrane production and signaling (Guo et al., Future Oncol 2014). Pharmacological targeting of SREBP-1, either through direct inhibition of its translocation or by blocking the proteases responsible for its maturation, represents a promising therapeutic approach for treating metabolic syndrome and various malignancies (Shao & Espenshade, Cell Metab 2012).

Other names

Sterol regulatory element-binding transcription factor 1SREBF1Adipocyte determination- and differentiation-dependent factor 1ADD1Basic helix-loop-helix domain-containing protein d1bHLHd1

Inhibition of SREBP-1 activation by preventing its translocation from the endoplasmic reticulum to the Golgi apparatus via SCAP binding, or by inhibiting the Site-1 (S1P) and Site-2 (S2P) proteases required for its proteolytic release into the nucleus.