Regulation of gene expression by SREBP and SCAP

Sterol regulatory element binding proteins (SREBPs) function as transcripti on factors that activate specific genes involved in cholesterol synthesis, endocytosis of low density lipoproteins, the synthesis of both saturated an d unsaturated fatty acids and glucose metabolism. As such, these proteins p rovide a link between lipid and carbohydrate metabolism. There are three SR EBPs, SREBP-1a, SREBP-1c and SREBP-2, that are encoded by two genes. SREBPs are synthesized as 125 kDa precursor proteins that are localized to the en doplasmic reticulum, The precursor is transported to the Golgi by a chapero ne protein (SREBP-cleavage activating protein) and then cleaved by two prot eases to release the mature, transcriptionally active 68 kDa amino terminal domain. Recent studies have shown that formation of mature SREBP is contro lled at multiple levels in response to changes in the levels of oxysterols, insulin/glucose and polyunsaturated fatty acids. These recent findings hav e important clinical implications relevant to hyperlipidemia and diabetes a nd are the topic of this review. (C) 2000 Elsevier Science B.V. All rights reserved.