Srebp

SREBP stands for "Sterol regulatory element-binding protein". 3 isoforms of SREBPs are known so far:

• SREBP1a
• SREBP1c and
• SREBP2.

The structurally similar proteins, play a decisive role and act as transcription factors in lipid biosynthesis.

SREBP2 is located in the membrane of the endoplasmic reticulum. The C- as well as the N-terminal domain, the protein consisting of 3 domains, protrude into the cytosol of the cell. The C-terminal domain binds in the membrane to a so-called scap (SREBP cleavage activating protein), which acts as a sensor for cholesterol in the membrane. The N-terminal domain is a transcription factor fixed in the membrane.

SREBPs can upregulate other genes when the cholesterol concentration within the cell drops and restore the balance within the line by increasing the uptake and simultaneously increasing the synthesis of cholesterol.

In case of an increased cholesterol concentration, the SREBP-Scap complex binds to a membrane protein (insig, insulin induced gene), which fixes SREBP2 in the membrane and prevents further transport.

Thus, at low cholesterol concentrations, SREBP2 is not fixed in the endoplasmic reticulum and can be transported to the Golgi apparatus. As a consequence, genes are expressed for proteins that are important for cholesterol metabolism (HMG-CoA reductase, the HMG-CoA synthase, the LDL receptor and prenyltransferase). These proteins are therefore only expressed at low cholesterol concentrations. They are self-regulatory, as their function increases the cholesterol concentration intracellularly, which again inhibits their own expression.

1. Shimano H (2001) Sterol regulatory element-binding proteins (SREBPs): transcriptional regulators of lipid synthetic genes. Prog Lipid Res 40:439-452.