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http://dx.doi.org/10.5352/JLS.2018.28.10.1233

SREBP as a Global Regulator for Lipid Metabolism  

Lee, Wonhwa (Aging Research Institute, Korea Research Institute of Bioscience and Biotechnology (KRIBB))
Seo, Young-kyo (Aging Research Institute, Korea Research Institute of Bioscience and Biotechnology (KRIBB))
Publication Information
Journal of Life Science / v.28, no.10, 2018 , pp. 1233-1243 More about this Journal
Abstract
Sterol regulatory-element binding proteins (SREBPs) are a family of transcription factors that regulate lipid homeostasis and metabolism by controlling the expression of enzymes required for endogenous cholesterol, fatty acid (FA), triacylglycerol, and phospholipid synthesis. The three SREBPs are encoded by two different genes. The SREBP1 gene gives rise to SREBP-1a and SREBP-1c, which are derived from utilization of alternate promoters that yield transcripts in which distinct first exons are spliced to a common second exon. SREBP-2 is derived from a separate gene. Additionally, SREBPs are implicated in numerous pathogenic processes, such as endoplasmic reticulum stress, inflammation, autophagy, and apoptosis. They also contribute to obesity, dyslipidemia, diabetes mellitus, and nonalcoholic fatty liver diseases. Genome-wide analyses have revealed that these versatile transcription factors act as important nodes of biological signaling networks. Changes in cell metabolism and growth are reciprocally linked through SREBPs. Anabolic and growth signaling pathways branch off and connect to multiple steps of SREBP activation and form complex regulatory networks. SREBPs are activated through the PI3K-Akt-mTOR pathway in these processes, but the molecular mechanism remains to be understood. This review aims to provide a comprehensive understanding of the role of SREBPs in physiology and pathophysiology at the cell, organ, and organism levels.
Keywords
Cellular homeostasis; lipid metabolism; lipotoxicity; SREBPs;
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