SREBP2 - regulating cholesterol homeostasis and lipid metabolism

Wed, 07/01/2015 - 14:47

Sterol regulatory element-binding proteins (SREBP) are important transcription factors regulating the synthesis and uptake of lipids including cholesterol. This essential role in lipid metabolism makes investigations into the functions SREBPs important for understanding metabolic disorders such as diabetes and may provide insight for future drug treatment strategies. SREBPs are basic helix-loop-helix (bHLH) leucine zipper transcription factors that bind to sterol response elements (SRE) to enhance the expression of target genes including LDL receptor and lipid synthesis genes. In humans there are two SREBP genes, SREBP1 and SREBP2. SREBP1 is expressed primarily in the liver while SREBP2 is ubiquitously expressed. SREBPs are synthesized as ER membrane proteins where they bind with SREBP cleavage-activating protein (SCAP), an important cholesterol sensor and transporter. This association with SCAP retains SREBP in the ER. Under low sterol conditions the SREBP-SCAP complex is transported to the Golgi where proteolytic cleavage of SREBP releases the N-terminal bHLH domain, allowing nuclear translocation and increased expression of target genes (1).

 SREBP2 antibodies are an important tool for monitoring this cleavage event and the cellular response to changing cholesterol levels. Kondo et al. used this strategy in their investigation of oxidative stress on lipid metabolism (2). Western blotting with the SREBP2 antibody allowed them to show a decrease in levels of mature SREBP2 in mice with mutations causing oxidative stress. Duan et al. used a similar strategy in their examination of PCSK9 and PPARγ dynamics on cholesterol homeostasis (3). Using the SREBP2 antibody, their study showed PPARγ activation lead to SREBP2 activation and increased LDLR expression. The effect of the gut microbiota on obesity and metabolism is an interesting area of research. In a study of germ-free mice Rabot et al. demonstrated a high-fat diet can increase sensitivity to insulin and alter cholesterol metabolism (4). By examining cell lysates with the SREBP2 antibody the authors showed an increase in nuclear SREBP2 and activation of cholesterol biosynthesis genes, indicating a role for gut microbiota in the regulation of cholesterol metabolism and insulin sensitivity. At the University of Utah the Schlegl group used the SREBP2 antibody to elucidate mechanisms of cholesterol lowering by polyunsaturated fatty acids (5). This study presents an explanation for the observed effect of diets rich in polyunsaturated fatty acids on lowered cholesterol and decreased incidence of cardiovascular disease.

Novus Biologicals offers SREBP2 reagents for your research needs including:


  1. 16525117
  2. 25003023
  3. 22593575
  4. 20724524
  5. 24057001

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