High resolution

Module 2: Figure sterol sensing

Sterol signalling at the endoplasmic reticulum (ER) membrane.

Sterols bind to the sterol regulatory element-binding proteins (SREBP) cleavage-activating protein (SCAP) resulting in the activation of site-1 protease (S1P), which then cleaves the SREBPs at a point on the luminal loop. A site-2 protease (S2P) then hydrolyses the N-terminal bHLH (basic helix–loop–helix) fragment to release the cytosolic portion, which then diffuses into the nucleus to initiate gene transcription. Reproduced from Brown, M.S. and Goldstein, J.L. (1999) A proteolytic pathway that controls the cholesterol content of membranes, cells, and blood. Proc. Natl. Acad. Sci. U.S.A. 96:11041–11048. Copyright (1999) National Academy of Sciences, U.S.A.; see Brown and Goldstein 1999).