Sterol-regulated transport of SREBPs from endoplasmic reticulum to Golgi: Oxysterols block transport by binding to Insig
Sterol-regulated transport of SREBPs from endoplasmic reticulum to Golgi: Oxysterols block transport by binding to Insig
复制标题
DOI：
10.1073/pnas.0700899104
复制
发表时间：
2007-04-17
影响因子：
11.1
通讯作者：
Goldstein, Joseph L.
中科院分区：
文献类型：
--
作者：
Radhakrishnan, Arun;Ikeda, Yukio;Goldstein, Joseph L.
动物体内胆固醇的合成受甾醇调节元件结合蛋白（SREBPs）从内质网转运到高尔基体的调控，在高尔基体中转录因子被蛋白水解以释放活性片段。运输被胆固醇或氧甾醇抑制，阻断胆固醇合成。胆固醇通过与srebp护送蛋白Scap结合而起作用，从而导致Scap与锚定蛋白Insigs结合。在这里，我们证明了氧化甾醇通过与Insigs结合而起作用，导致Insigs与Scap结合。对insg的6个跨膜螺旋的突变分析表明，insg与氧化甾醇和Scap结合的第3和第4个螺旋是重要的。这些研究将insg定义为氧甾醇结合蛋白，解释了氧甾醇抑制动物细胞中胆固醇合成的长期已知能力。
Cholesterol synthesis in animals is controlled by the regulated transport of sterol regulatory element-binding proteins (SREBPs) from the endoplasmic reticulum to the Golgi, where the transcription factors are processed proteolytically to release active fragments. Transport is inhibited by either cholesterol or oxysterols, blocking cholesterol synthesis. Cholesterol acts by binding to the SREBP-escort protein Scap, thereby causing Scap to bind to anchor proteins called Insigs. Here, we show that oxysterols act by binding to Insigs, causing Insigs to bind to Scap. Mutational analysis of the six transmembrane helices of Insigs reveals that the third and fourth are important for Insig's binding to oxysterols and to Scap. These studies define Insigs as oxysterol-binding proteins, explaining the long-known ability of oxysterols to inhibit cholesterol synthesis in animal cells.