The Study Of The SREBPs

Sterol Regulatory Element Binding proteins (SREBPs), membrane-bound transcription factors that activate at least 30 genes encoding enzymes of lipogenesis and adipogenesis. SREBPs are embedded in membranes of the endoplasmic reticulum and the nuclear envelope. These membrane proteins are members of the bHLH-Zip (basic helix-loop-helix-leucine zipper) family of transcription factors.Three different SREBPs are known, SREBPs-1a, -1c and -2. SREBPs are synthesized as precursor proteins in the endoplasmic reticulum , where they form a complex with another protein, SREBP cleavage activating protein (SCAP ). The SCAP molecule contains a sterol sensory domain. In the feedback regulation system of cholesterol metabolism, SCAP together with SREBPs control transcription of the genes encoding enzymes of cholesterol and fatty acid biosynthesis. Adipocyte determination differentiation factor (ADD)-1 is the homologue of human SREBP-1c. ADD1/SREBP-1c controlled the adipocyte differentiation with peroxisome proliferator-activated receptor(PPAR) ,CCAAT/enhancer binding protein (C/EBPs ). Besides the regulation of SREBPs by metabolites and nutrients, these transcription factors are also targets of hormones (like insulin and leptin), growth factors, inflammatory signals, and drugs. We have recently shown that SREBP-1 might play a role in the development of cellular features belonging to lipid toxicity and possibly metabolism syndrome . Thus, the metabolic syndrome appears to be not only a disease or state of altered glucose tolerance, plasma lipid levels, blood pressure, and body fat distribution, but rather a complex clinical phenomenon of dysregulated gene expression.