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Sterol regulatory element-binding proteins (SREBPs) are transcription factors that are members of the basic helix-loop-helix leucine zipper family of DNA binding proteins. Three isoforms have been identified in mammalian tissues that vary in structure, regulation, and function. SREBP-1a and SREBP-1c (originally cloned as ADD1) are protein products of alternative promoter usage of the SREBP-1 gene. The third isoform is transcribed from a different gene, SREBP-2. SREBPs are present as 120 kDa inactive precursors in the endoplasmic reticulum (ER) membrane. Upon activation, the SREBP protein is translocated to the Golgi and proteolytic cleavage occurs resulting in a mature transcriptionally active 60-78 kDa fragment. In liver and adipose tissues, SREBPs have a significant influence on lipid and cholesterol accumulation by inducing the transcription of genes involved in these processes. While SREBP-1 is thought to be more important in regulating the expression of genes involved in triglyceride synthesis and accumulation, SREBP-2 has been more closely linked to those involved in cholesterol synthesis and accumulation.
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