Molecular regulation of SREBP function: the Insig-SCAP connection and isoform-specific modulation of lipid synthesis.
Sterol regulatory element binding proteins (SREBPs) are a family of membrane-bound transcription factors that play a unique and fundamental role in both cholesterol and fatty acid metabolism, relevant to human disease. There are three SREBPs that regulate the expression of over 30 genes. SREBPs are subject to regulation at three levels: proteolytic cleavage, rapid degradation by the ubiquitin-proteasome pathway, and sumoylation. Recently, there have been exciting advances in our understanding of the molecular mechanism of SREBP trafficking and processing with new information on the role of insulin-induced genes and the differential role and regulation of SREBP-1c and -2, which may ultimately lead to novel strategies for the treatment of dyslipidemia and insulin resistance.
McPherson
Ruth
R
Lipoprotein and Atherosclerosis Group, University of Ottawa Heart Institute, ON, Canada. rmcpherson@ottawaheart.ca
Gauthier
Andre
A
D000818:Animals; D022762:CCAAT-Enhancer-Binding Proteins / Q000235:genetics / Q000502:physiology*; D002352:Carrier Proteins / Q000502:physiology*; D002784:Cholesterol / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000235:genetics / Q000502:physiology*; D005227:Fatty Acids / Q000378:metabolism; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins; D008055:Lipids / Q000096:biosynthesis* / Q000235:genetics; D008565:Membrane Proteins / Q000502:physiology*; D023421:Models, Animal; D008954:Models, Biological; D051780:Sterol Regulatory Element Binding Protein 1; D051782:Sterol Regulatory Element Binding Protein 2; D014157:Transcription Factors / Q000235:genetics / Q000502:physiology*
D022762:CCAAT-Enhancer-Binding Proteins; D002352:Carrier Proteins; D004268:DNA-Binding Proteins; D005227:Fatty Acids; C108626:INSIG1 protein, human; C467727:INSIG2 protein, human; D047908:Intracellular Signaling Peptides and Proteins; D008055:Lipids; D008565:Membrane Proteins; C497387:SREBF1 protein, human; C497390:SREBF2 protein, human; C102196:SREBP cleavage-activating protein; D051780:Sterol Regulatory Element Binding Protein 1; D051782:Sterol Regulatory Element Binding Protein 2; D014157:Transcription Factors; D002784:Cholesterol