Crucial Step in Cholesterol Homeostasis: Sterols Promote Binding of SCAP to INSIG-1, a Membrane Protein that Facilitates Retention of SREBPs in ER

Tong Yang; Peter J. Espenshade; Michael E. Wright; Daisuke Yabe; Yi Gong; Ruedi Aebersold; Joseph L. Goldstein; Michael S. Brown

doi:10.1016/S0092-8674(02)00872-3

Back

Crucial Step in Cholesterol Homeostasis: Sterols Promote Binding of SCAP to INSIG-1, a Membrane Protein that Facilitates Retention of SREBPs in ER

Journal article

Open access

Peer reviewed

Crucial Step in Cholesterol Homeostasis: Sterols Promote Binding of SCAP to INSIG-1, a Membrane Protein that Facilitates Retention of SREBPs in ER

Tong Yang, Peter J. Espenshade, Michael E. Wright, Daisuke Yabe, Yi Gong, Ruedi Aebersold, Joseph L. Goldstein and Michael S. Brown

Cell, Vol.110(4), pp.489-500

2002

DOI: 10.1016/S0092-8674(02)00872-3

PMID: 12202038

Files and links (1)

url

https://doi.org/10.1016/S0092-8674(02)00872-3View

Published (Version of record) Open Access

Abstract

Using coimmunoprecipitation and tandem mass spectrometry, we identify INSIG-1 as an ER protein that binds the sterol-sensing domain of SREBP cleavage-activating protein (SCAP) and facilitates retention of the SCAP/SREBP complex in the ER. In sterol-depleted cells, SCAP escorts SREBPs from ER to Golgi for proteolytic processing, thereby allowing SREBPs to stimulate cholesterol synthesis. Sterols induce binding of SCAP to INSIG-1, as determined by blue native-PAGE, and this is correlated with the inhibition of SCAP exit from the ER. Overexpression of INSIG-1 increases the sensitivity of cells to sterol-mediated inhibition of SREBP processing. Mutant SCAP(Y298C) fails to bind INSIG-1 and is resistant to sterol-mediated inhibition of ER exit. By facilitating sterol-dependent ER retention of SCAP, INSIG-1 plays a central role in cholesterol homeostasis.

Details

Title: Subtitle: Crucial Step in Cholesterol Homeostasis: Sterols Promote Binding of SCAP to INSIG-1, a Membrane Protein that Facilitates Retention of SREBPs in ER
Creators: Tong Yang - The University of Texas Southwestern Medical Center
Peter J. Espenshade - The University of Texas Southwestern Medical Center
Michael E. Wright - Institute for Systems Biology
Daisuke Yabe - The University of Texas Southwestern Medical Center
Yi Gong - The University of Texas Southwestern Medical Center
Ruedi Aebersold - Institute for Systems Biology
Joseph L. Goldstein - The University of Texas Southwestern Medical Center
Michael S. Brown - The University of Texas Southwestern Medical Center
Resource Type: Journal article
Publication Details: Cell, Vol.110(4), pp.489-500
DOI: 10.1016/S0092-8674(02)00872-3
PMID: 12202038
NLM abbreviation: Cell
ISSN: 0092-8674
eISSN: 1097-4172
Publisher: Elsevier Inc
Language: English
Date published: 2002
Academic Unit: Molecular Physiology and Biophysics
Record Identifier: 9984297502002771

Metrics

15 Record Views

847 Times Cited - Web of Science

See more details