Sterol regulatory element-binding proteins (SREBPs): transcriptional regulators of lipid synthetic genes.
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.
Shimano
H
H
Department of Internal Medicine, Institute of Clinical Medicine, University of Tsukuba, 1-1-1 Tennodai, Tsukuba, Ibaraki 305-8575, Japan. shimano-tky@Umin.ac.jp
D000818:Animals; D022762:CCAAT-Enhancer-Binding Proteins / Q000235:genetics / Q000502:physiology*; D002462:Cell Membrane / Q000378:metabolism; D002784:Cholesterol / Q000096:biosynthesis / Q000235:genetics; D004268:DNA-Binding Proteins / Q000235:genetics / Q000502:physiology*; D024721:E-Box Elements; D005227:Fatty Acids / Q000378:metabolism; D005656:Fungal Proteins; D050980:GATA Transcription Factors; D005786:Gene Expression Regulation / Q000187:drug effects / Q000502:physiology*; D005947:Glucose / Q000494:pharmacology; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000494:pharmacology; D007328:Insulin / Q000494:pharmacology; D047908:Intracellular Signaling Peptides and Proteins; D050356:Lipid Metabolism; D008055:Lipids / Q000096:biosynthesis*; D008099:Liver / Q000378:metabolism*; D008565:Membrane Proteins / Q000378:metabolism; D051379:Mice; D018345:Mice, Knockout; D008822:Mice, Transgenic; D011401:Promoter Regions, Genetic / Q000235:genetics; D051780:Sterol Regulatory Element Binding Protein 1; D014157:Transcription Factors; D014158:Transcription, Genetic
D022762:CCAAT-Enhancer-Binding Proteins; D004268:DNA-Binding Proteins; D005227:Fatty Acids; D005656:Fungal Proteins; D050980:GATA Transcription Factors; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D007328:Insulin; D047908:Intracellular Signaling Peptides and Proteins; D008055:Lipids; D008565:Membrane Proteins; C497387:SREBF1 protein, human; C102196:SREBP cleavage-activating protein; C115209:Sre protein, Neurospora crassa; C497388:Srebf1 protein, mouse; D051780:Sterol Regulatory Element Binding Protein 1; D014157:Transcription Factors; D002784:Cholesterol; D005947:Glucose