College of Veterinary Medicine, South China Agricultural University, No,483 Wu Shan Road, Tian He District, Guangzhou, 510642, China.
Lipids Health Dis. 2012 Dec 18;11:173. doi: 10.1186/1476-511X-11-173.
The molecular mechanism of how cells maintain cholesterol homeostasis has become clearer for the understanding of complicated association between sterol regulatory element-binding proteins (SREBPs), SREBP cleavage-activating protein (SCAP), 3-hydroxy-3-methylglutaryl coenzyme A reductase (HMG-CoA reductase) and Insuin induced-genes (Insigs). The pioneering researches suggested that SREBP activated the transcription of genes encoding HMG-CoA reductase and all of the other enzymes involved in the synthesis of cholesterol and lipids. However, SREBPs can not exert their activities alone, they must form a complex with another protein, SCAP in the endoplasmic reticulum (ER) and translocate to Golgi. Insigs are sensors and mediators that regulate cholesterol homeostasis through binding to SCAP and HMG-CoA reductase in diverse tissues such as adipose tissue and liver, as well as the cultured cells. In this article, we aim to review on the dual functions of Insig protein family in cholesterol homeostasis.
细胞如何维持胆固醇稳态的分子机制已逐渐明晰,这有助于我们理解固醇调节元件结合蛋白(SREBPs)、SREBP 切割激活蛋白(SCAP)、3-羟-3-甲基戊二酰辅酶 A 还原酶(HMG-CoA 还原酶)和胰岛素诱导基因(Insigs)之间复杂的关联。开创性的研究表明,SREBP 激活了编码 HMG-CoA 还原酶和胆固醇及脂质合成中所有其他酶的基因的转录。然而,SREBPs 不能单独发挥作用,它们必须与内质网(ER)中的另一种蛋白质 SCAP 形成复合物,并易位到高尔基体。Insigs 是传感器和介质,通过与脂肪组织和肝脏等不同组织以及培养细胞中的 SCAP 和 HMG-CoA 还原酶结合,调节胆固醇稳态。本文旨在综述 Insig 蛋白家族在胆固醇稳态中的双重功能。