sterol response element binding

Definition

Target type: molecularfunction

Binding to a sterol response element (SRE), a nonpalindromic sequence found in the promoters of genes involved in lipid metabolism. [GOC:vk, PMID:11994399]

Sterol response element binding (SREBP) is a crucial molecular function in regulating lipid metabolism, particularly cholesterol homeostasis. SREBPs are transcription factors that sense cellular sterol levels and activate the expression of genes involved in cholesterol synthesis, uptake, and efflux.

The process begins with SREBPs residing in the endoplasmic reticulum (ER) membrane as inactive precursors. When cellular sterol levels are low, SREBPs are escorted to the Golgi apparatus via a protein complex that includes SREBP cleavage-activating protein (SCAP). In the Golgi, two proteases, S1P and S2P, cleave SREBP, releasing its active N-terminal domain. This domain translocates to the nucleus and binds to specific DNA sequences called sterol response elements (SREs) located in the promoter regions of target genes.

Upon binding to SREs, SREBPs recruit other transcription factors and co-activators, forming a complex that activates gene transcription. These target genes encode enzymes involved in cholesterol biosynthesis, such as HMG-CoA reductase, as well as proteins that facilitate cholesterol uptake (LDL receptor) and efflux (ABCA1).

By activating these genes, SREBPs increase cholesterol synthesis and uptake, replenishing cellular sterol levels. When sterol levels rise, SREBPs are inhibited, reducing the expression of target genes and restoring cholesterol homeostasis.

Therefore, SREBP binding serves as a critical regulatory mechanism for maintaining lipid homeostasis by orchestrating the expression of genes involved in cholesterol synthesis, uptake, and efflux in response to cellular sterol levels.'
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Proteins (2)

Compounds (31)