Department of Molecular Genetics, University of Texas Southwestern Medical Center, Dallas, Texas 75390, USA.
Cold Spring Harb Perspect Biol. 2011 Jul 1;3(7):a004754. doi: 10.1101/cshperspect.a004754.
In mammals, intracellular levels of cholesterol and fatty acids are controlled through a feedback regulatory system mediated by a family of transcription factors called sterol regulatory element-binding proteins (SREBPs). SREBPs are synthesized as inactive precursors bound to membranes of the endoplasmic reticulum. When cells are deprived of cholesterol and fatty acids, NH(2)-terminal fragments of SREBPs become proteolytically released from membranes and migrate to the nucleus to activate transcription of genes required for lipid synthesis and uptake. Conversely, lipid repletion inhibits proteolytic processing of SREBPs and thereby suppresses lipid accumulation. We review here studies in cultured cells that reveal the mechanism for regulation of SREBP proteolytic activation, and those in animal models in which SREBP proteolysis has been either activated or inhibited to show the essential role of SREBPs in regulating hepatic lipid homeostasis.
在哺乳动物中，胆固醇和脂肪酸的细胞内水平通过一种称为固醇调节元件结合蛋白（SREBPs）的转录因子家族介导的反馈调节系统来控制。SREBPs 作为与内质网膜结合的无活性前体被合成。当细胞缺乏胆固醇和脂肪酸时，SREBP 的 NH2-末端片段从膜上被蛋白水解释放出来，并迁移到细胞核中，激活脂质合成和摄取所需基因的转录。相反，脂质补充抑制 SREBP 的蛋白水解加工，从而抑制脂质积累。在这里，我们综述了培养细胞中揭示 SREBP 蛋白水解激活调节机制的研究，以及动物模型中 SREBP 蛋白水解被激活或抑制的研究，以显示 SREBPs 在调节肝脏脂质动态平衡中的重要作用。
