Sterol Regulatory Element Binding Transcription Factor 2 (SREBF2)

SREBF2 encodes a ubiquitously expressed transcription factor that controls cholesterol homeostasis by stimulating transcription of sterol-regulated genes. The encoded protein contains a basic helix-loop-helix-leucine zipper (bHLH-Zip) domain.

SCAP escorts SREBPs from the endoplasmic reticulum (ER) to the Golgi, where SREBPs are cleaved by site-1 protease (S1P). The authors showed that sterols block this transport and abolish cleavage. Relocating active S1P from Golgi to ER by treating cells with brefeldin A or by fusing the ER retention signal KDEL to S1P obviated the SCAP requirement and rendered cleavage insensitive to sterols.