Sterol regulatory element-binding protein 1


Sterol regulatory element-binding transcription factor 1 also known as sterol regulatory element-binding protein 1 is a protein that in humans is encoded by the SREBF1 gene.
This gene is located within the Smith–Magenis syndrome region on chromosome 17. Two transcript variants encoding different isoforms have been found for this gene. The isoforms are SREBP-1a and SREBP-1c. SREBP-1a is expressed in the intestine and spleen, whereas SREBP-1c is mainly expressed in liver, muscle, and fat.

Expression

The proteins encoded by this gene are transcription factors that bind to a sequence in the promoter of different genes, called sterol regulatory element-1. This element is a decamer flanking the LDL receptor gene and other genes involved in, for instance, sterol biosynthesis. The protein is synthesized as a precursor that is attached to the nuclear membrane and endoplasmic reticulum. Following cleavage, the mature protein translocates to the nucleus and activates transcription by binding to the SRE1. Sterols inhibit the cleavage of the precursor, and the mature nuclear form is rapidly catabolized, thereby reducing transcription. The protein is a member of the basic helix-loop-helix-leucine zipper transcription factor family.
SREBP-1a regulates genes related to lipid and cholesterol production and its activity is regulated by sterol levels in the cell.
SREBP-1a and SREBP-1c are both encoded by the same gene, but are transcribed by different promoters. For animals in a fasted state, SREBP-1c expression is suppressed in the liver, but a high carbohydrate meal strongly induces SREBP-1c expression.

Function

SREBP-1 plays a key role in the induction of lipogenesis by the liver. mTORC1 is activated by insulin leading to increased production of SBREP-1c, which facilitates storage of fatty acids as triglycerides.

Clinical relevance

SREBP-1c regulates genes required for glucose metabolism and fatty acid and lipid production and its expression is induced by insulin. Insulin-stimulated SREBP-1c increases glycolysis by activation of glucokinase enzyme, and increases lipogenesis. Insulin stimulation of SREBP-1c is mediated by liver X receptor and mTORC1.
High blood levels of insulin due to insulin resistance often leads to steatosis in the liver because of SREBP-1 activation. Suppression of SREBP-1c by sirtuin 1 or by other means protects against development of fatty liver.
SREBP-1 is highly activated in cancers because tumor cells require lipids for cell membranes, second messengers, and energy.

Interactions

SREBF1 has been shown to interact with: