SREBP

SREBPs (sterol regulatory element-binding proteins) are membrane bound transcription factors that are essential in the regulation of cholesterol, fatty acid and triglyceride biosynthesis. There are two SREBP genes in mammals, SREBP-1 and SREBP-2.

Products
Background
Literature
Pathways
Gene Data

Inhibitors

Cat No Product Name / Activity
4444 Fatostatin A
Cell permeable inhibitor of SREBP activation
3354 PF 429242
Competitive inhibitor of SREBP site 1 protease

SREBPs (sterol regulatory element-binding proteins) are membrane bound transcription factors that are essential in the regulation of cholesterol, fatty acid and triglyceride biosynthesis. There are two SREBP genes in mammals, SREBP-1, which is most abundant in the liver and adrenal glands, and SREBP-2, which is ubiquitously expressed. In addition, SREBP-1 encodes two different isoforms of the protein, SREBP-1a and SREBP-1c, expression of which is dependent on the promoter. The proteins form a subgroup of the larger class of bHLHZ (basic-helix loop-helix leucine zipper domain) transcription factors. SREBP-1c primarily regulates fatty acid metabolism, including the fatty acid synthase (FASN) gene, SREBP-2 is primarily responsible for cholesterol metabolism-related genes, including HMG-CoA reductase, while SREBP-1a targets both.

SREBPs are synthesized as inactive precursors bound to the endoplasmic reticulum (ER). When intracellular cholesterol levels are low, SREBP cleavage activating protein (SCAP), which acts as a cholesterol sensor, transports SREBP from the ER to the Golgi apparatus, where it is cleaved by site-1 protease (S1P). The amino-terminal bHLHZ domain is then further cleaved by site-2 protease (S2P) giving rise to nSREBP (or nuclear SREBP), which translocates to the nucleus where it activates transcription. SREBP-1a appears to be constitutively expressed at low levels, whereas expression of SREBP-1c and SREBP-2 is regulated by a feed-forward loop whereby nSREBPs activate transcription of their own genes. SREBP-1c is also regulated by liver X receptors, insulin and glucagon.

Insulin stimulates the production of fatty acids in the liver at times of carbohydrate excess. Evidence suggests that this effect of insulin is mediated by SREBP-1c via the PI 3-kinase/Akt signaling pathway, and that the fatty liver associated with insulin resistance is due to elevated SREBP-1c levels. Drugs targeting SREBP may therefore have potential to treat metabolic disorders, such as type II diabetes and insulin resistance, as well as atherosclerosis. SREBP could also be a potential target in cancer therapy, since cancer cells require increased lipogenesis for growth and proliferation.

Literature for SREBP

Cancer

Cancer Research Product Guide

A collection of over 750 products for cancer research, the guide includes research tools for the study of:

  • Cancer Metabolism
  • Epigenetics in Cancer
  • Receptor Signaling
  • Cell Cycle and DNA Damage Repair
  • Angiogenesis
  • Invasion and Metastasis
Cardiovascular

Cardiovascular Research Product Guide

A collection of over 250 products for cardiovascular research, the guide includes research tools for the study of:

  • Hypertension
  • Thrombosis and Hemostasis
  • Atherosclerosis
  • Myocardial Infarction
  • Ischemia/Reperfusion Injury
  • Arrhythmias
  • Heart Failure
Cancer Metabolism

Cancer Metabolism Poster

Adapted from the 2015 Cancer Product Guide, Edition 3, this poster summarizes the main targets for cancer metabolism researchers. Genetic changes and epigenetic modifications in cancer cells alter the regulation of cellular metabolic pathways. These distinct metabolic circuits could provide viable cancer therapeutic targets.

Cardiovascular

Cardiovascular Poster

Cardiovascular disease remains one of the major causes of morbidity and mortality in the Western world and therefore this therapeutic area continues to be of great interest to researchers. This poster highlights the key GPCRs regulating vascular reactivity.

Pathways for SREBP

Insulin

Insulin Signaling Pathway

Signaling through the insulin pathway is fundamental for the regulation of intracellular glucose levels. This pathway can become dysregulated in diabetes.

SREBP Gene Data

Gene Species Gene Symbol Gene Accession No. Protein Accession No.
SREBF1 Human SREBF1 NM_004176 P36956
Mouse Srebf1 NM_011480 Q9WTN3
Rat Srebf1 NM_001276707 P56720
SREBF2 Human SREBF2 NM_004599 Q12772
Mouse Srebf2 NM_033218 Q3U1N2
Rat Srebf2 NM_001033694 Q3T1I5