The sterol regulatory element-binding protein pathway: control of lipid homeostasis through regulated intracellular transport.
The sterol regulatory element-binding proteins (SREBPs) are membrane-bound transcription factors that play a central role in cellular lipid homeostasis through the end-product feedback regulation of lipid synthesis. This feedback pathway is best understood in the case of cholesterol. Accumulation of cholesterol suppresses the proteolytic release of the transcriptionally active amino-terminal fragment of SREBP from the membrane-bound precursor. Experiments reported during the past year have led to a more complete understanding of the mechanisms that regulate the processing of SREBPs and their role in cellular lipid homeostasis. Regulation of lipid homeostasis is intimately associated with intracellular membrane trafficking; SREBPs undergo regulated transport from the endoplasmic reticulum to the Golgi apparatus in response to cellular lipid demand. The regulated step in this transport is the budding of a complex of SREBP and SREBP cleavage-activating protein into vesicles. In the present review we focus on recent results that give a more detailed picture of the mechanisms that are involved in end-product feedback regulation of lipid homeostasis.
Sakai
J
J
Division of Nephrology, Endocrinology, and Vascular Medicine, Department of Medicine, Tohoku University Graduate School of Medicine, Sendai, Japan.
Rawson
R B
RB
D000818:Animals; D001692:Biological Transport; D022762:CCAAT-Enhancer-Binding Proteins / Q000378:metabolism* / Q000502:physiology*; D004268:DNA-Binding Proteins / Q000378:metabolism* / Q000502:physiology*; D004721:Endoplasmic Reticulum / Q000378:metabolism; D006056:Golgi Apparatus / Q000378:metabolism; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins; D050356:Lipid Metabolism; D008565:Membrane Proteins / Q000378:metabolism; D008954:Models, Biological; D017434:Protein Structure, Tertiary; D051780:Sterol Regulatory Element Binding Protein 1; D014157:Transcription Factors / Q000378:metabolism
D022762:CCAAT-Enhancer-Binding Proteins; D004268:DNA-Binding Proteins; D047908:Intracellular Signaling Peptides and Proteins; D008565:Membrane Proteins; C497387:SREBF1 protein, human; C102196:SREBP cleavage-activating protein; D051780:Sterol Regulatory Element Binding Protein 1; D014157:Transcription Factors