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Published on: May 12, 2023
Sterol regulatory element-binding proteins (SREBPs): transcriptional regulators of lipid synthetic genes
1Department of Internal Medicine, Institute of Clinical Medicine, University of Tsukuba, 1-1-1 Tennodai, Tsukuba, Ibaraki 305-8575, Japan. shimano-tky@Umin.ac.jp
Abstract:
Roles of sterol regulatory element-binding proteins (SREBPs) have been established as lipid synthetic transcription factors especially for cholesterol and fatty acid synthesis. SREBPs have unique characteristics. Firstly, they are membrane-bound proteins and the N-terminal active portions enter nucleus to activate their target genes after proteolytic cleavage, which requires sterol-sensing molecule, SREBP-activating protein (SCAP) and is crucial for sterol-regulation. Secondly, they bind and activate sterol-regulatory (SREs) containing promoters as well as some E-boxes, which makes SREBPs eligible to regulate a wide range of lipid genes. Finally, three isoforms, SREBP-1a-1c, and have different roles in lipid synthesis. In vivo studies using transgenic and knockout mice suggest that SREBP-1 seems to be involved in energy metabolism including fatty acid and glucose/insulin metabolism, whereas SREBP-2 is specific to cholesterol synthesis. Future studies will be focused on understanding molecular mechanisms sensing cellular sterol and energy states where SREBPs are deeply involved.
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