SREBPs: the crossroads of physiological and pathological lipid homeostasis.
The uptake, biosynthesis and metabolism of cholesterol and other lipids are exquisitely regulated by feedback and feed-forward pathways in organisms ranging from Caenorhabditis elegans to humans. As endoplasmic reticulum (ER) membrane-embedded transcription factors that are activated in the Golgi apparatus, sterol regulatory element-binding proteins (SREBPs) are central to the intracellular surveillance of lipid catabolism and de novo biogenesis. The biosynthesis of SREBP proteins, their migration from the ER to the Golgi compartment, intra-membrane proteolysis, nuclear translocation and trans-activation potential are tightly controlled in vivo. Here we summarize recent studies elucidating the transcriptional and post-transcriptional regulation of SREBP-1c through nutrition and the action of hormones, particularly insulin, and the resulting implications for dyslipidemia of obesity, metabolic syndrome and type 2 diabetes.
Raghow
Rajendra
R
Department of Pharmacology, University of Tennessee Health Science Center, 874 Union Avenue, Memphis, TN 38163, USA. rraghow@utmem.edu
Yellaturu
Chandrahasa
C
Deng
Xiong
X
Park
Edwards A
EA
Elam
Marshall B
MB
D000818:Animals; D001483:Base Sequence; D000242:Cyclic AMP / Q000494:pharmacology; D004721:Endoplasmic Reticulum / Q000378:metabolism; D005786:Gene Expression Regulation / Q000187:drug effects; D005934:Glucagon / Q000494:pharmacology; D006056:Golgi Apparatus / Q000378:metabolism; D006706:Homeostasis / Q000235:genetics; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000502:physiology; D050356:Lipid Metabolism / Q000235:genetics*; D052439:Lipid Metabolism Disorders / Q000235:genetics*; D008055:Lipids / Q000494:pharmacology; D008565:Membrane Proteins / Q000502:physiology; D008954:Models, Biological; D008969:Molecular Sequence Data; D011499:Protein Processing, Post-Translational / Q000187:drug effects / Q000502:physiology; D021381:Protein Transport / Q000187:drug effects; D012689:Sequence Homology, Nucleic Acid; D051779:Sterol Regulatory Element Binding Proteins / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism / Q000502:physiology*
C108626:INSIG1 protein, human; C467727:INSIG2 protein, human; D047908:Intracellular Signaling Peptides and Proteins; D008055:Lipids; D008565:Membrane Proteins; D051779:Sterol Regulatory Element Binding Proteins; D005934:Glucagon; D000242:Cyclic AMP