Lipid homeostasis in vertebrate cells is regulated by a family of basic helix-loop-helix (HLH) transcription factors called sterol regulatory element binding proteins (SREBPs). SREBPs directly activate the expression of over 30 genes involved in both the synthesis and uptake of cholesterol, fatty acids, triglycerides, and phospholipids.^1,2 SREBP-2 regulates cholesterol synthesis by activating the transcription of genes for HMG-CoA reductase and other enzymes of the cholesterol synthetic pathway.³ It is also involved in activating genes required to generate NADPH, which is consumed at multiple stages in cholesterol biosynthesis. SREBP-2 is ubiquitously expressed.⁴ Cayman’s SREBP-2 Cell-Based Translocation Assay Kit provides the tools needed to study SREBP-2 movement within whole cells. The kit contains a highly specific SREBP-2 primary antibody together with a DyLight^™ (trademarked by Pierce Biotechnology Inc.) conjugated secondary antibody in a ready to use format. Also included as a positive control is a cholesterol trafficking inhibitor, U18666A, which has been shown to activate SREBP-2 translocation into nuclei by scientists at Cayman Chemical Company.

1 Osborne, T.F. Sterol regulatory element-binding proteins (SREBP’s): Key regulators of nutritional homeostasis and insulin action. J Biol Chem 275(42) 32379-32382 (2000).

2 Lin, J., Yang, R., Tarr, P.T., et al. Hyperlipidemic effects of dietary saturated fats mediated through PGC-1β coactivation of SREBP. Cell 120 261-273 (2005).

3 Sakai, J., Nohturfft, A., Goldstein, J.L., et al. Cleavage of sterol regulatory element-binding proteins (SREBPs) at site-1 requires interaction with SREBP cleavage-activating protein. Evidence from in vivo competition studies. J Biol Chem 273(10) 5785-5793 (1998).

4 Iizuka, K., Bruick, R.K., Liang, G., et al. Deficiency of carbohydrate response element-binding protein (ChREBP) reduces lipogenesis as well as glycolysis. Proc Natl Acad Sci USA 101(19) 7281-7286 (2004).

Osborne, T.F. Sterol regulatory element-binding proteins (SREBP’s): Key regulators of nutritional homeostasis and insulin action. J Biol Chem 275(42) 32379-32382 (2000).

Sakai, J., Nohturfft, A., Goldstein, J.L., et al. Cleavage of sterol regulatory element-binding proteins (SREBPs) at site-1 requires interaction with SREBP cleavage-activating protein. Evidence from in vivo competition studies. J Biol Chem 273(10) 5785-5793 (1998).

Lin, J., Yang, R., Tarr, P.T., et al. Hyperlipidemic effects of dietary saturated fats mediated through PGC-1β coactivation of SREBP. Cell 120 261-273 (2005).

Brown, M.S., Goldstein, J.L. The SREBP pathway: Regulation of cholesterol metabolism by proteolysis of a membrane-bound transcription factor. Cell 89 331-340 (1997).

Iizuka, K., Bruick, R.K., Liang, G., et al. Deficiency of carbohydrate response element-binding protein (ChREBP) reduces lipogenesis as well as glycolysis. Proc Natl Acad Sci USA 101(19) 7281-7286 (2004).

Smith, L.H., Petrie, M.S., Morrow, J.D., et al. 7The sterol response element binding protein regulates cyclooxygenase-2 gene expression in endothelial cells. J Lipid Res 46 862-871 (2005).

Matsuda, M., Korn, B.S., Hammer, R.E., et al. SREBP cleavage-activating protein (SCAP) is required for increased lipid synthesis in liver induced by cholesterol deprivation and insulin elevation. Genes Dev 15 1206-1216 (2001).

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