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.
journal_name
Proc Natl Acad Sci U S Aauthors
Radhakrishnan A,Ikeda Y,Kwon HJ,Brown MS,Goldstein JLdoi
10.1073/pnas.0700899104subject
Has Abstractpub_date
2007-04-17 00:00:00pages
6511-8issue
16eissn
0027-8424issn
1091-6490pii
0700899104journal_volume
104pub_type
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