Molecular aspects in feedback regulation of gene expression by cholesterol in mammalian cells

Intracellular cholesterol balance is maintained by a tight feedback mechanism that prevents the overaccumulation of cholesterol to cytotoxic levels. This is achieved through the coordinate regulation of genes of cholesterol uptake and biosynthesis by the sterol regulatory element binding proteins (SREBPs). The SREBPs are synthesized as membrane bound precursors that are released from their membrane tether when the cell needs new cholesterol. In the present article we present a model for how the cholesterol uptake pathway may be activated before the biosynthetic pathway to prevent wasting cellular energy and carbon on unneeded synthesis. Then we introduce a system for analyzing the differential localization and cellular trafficking of the different SREBP isoforms that can be performed over time in living cells. (C) 1998 Academic Press.