Sterol-regulated transport of SREBPs from endoplasmic reticulum to Golgi: Oxysterols block transport by binding to Insig
Top Cited Papers
- 17 April 2007
- journal article
- Published by Proceedings of the National Academy of Sciences in Proceedings of the National Academy of Sciences of the United States of America
- Vol. 104 (16), 6511-6518
- https://doi.org/10.1073/pnas.0700899104
Abstract
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.Keywords
This publication has 47 references indexed in Scilit:
- Sterol-regulated transport of SREBPs from endoplasmic reticulum to Golgi: Insig renders sorting signal in Scap inaccessible to COPII proteinsProceedings of the National Academy of Sciences of the United States of America, 2007
- Juxtamembranous aspartic acid in Insig-1 and Insig-2 is required for cholesterol homeostasisProceedings of the National Academy of Sciences of the United States of America, 2006
- Protein Sensors for Membrane SterolsCell, 2006
- Insig Required for Sterol-mediated Inhibition of Scap/SREBP Binding to COPII Proteins in Vitro*♦Journal of Biological Chemistry, 2005
- Insig-mediated degradation of HMG CoA reductase stimulated by lanosterol, an intermediate in the synthesis of cholesterolCell Metabolism, 2005
- Cholesterol and 25-Hydroxycholesterol Inhibit Activation of SREBPs by Different Mechanisms, Both Involving SCAP and InsigsPublished by Elsevier BV ,2004
- BI-DIRECTIONAL PROTEIN TRANSPORT BETWEEN THE ER AND GOLGIAnnual Review of Cell and Developmental Biology, 2004
- Cholesterol Addition to ER Membranes Alters Conformation of SCAP, the SREBP Escort Protein that Regulates Cholesterol MetabolismMolecular Cell, 2002
- Crucial Step in Cholesterol HomeostasisCell, 2002
- Regulated Intramembrane ProteolysisCell, 2000