The BioGRID | PUBLICATION VIEW

	EMBO J. Nov (2005); 24(22):3917-26
INSIG- a broadly conserved transmembrane chaperone for sterol-sensing domain proteins-
Flury I, Garza R, Shearer A, Rosen J, Cronin S, Hampton RY
Section of Cell and Development Biology, UCSD Division of Biological Sciences, La Jolla, CA 92093, USA-
Abstract: INSIGs are proteins that underlie sterol regulation of the mammalian proteins SCAP -SREBP cleavage activating protein- and HMG-CoA reductase -HMGR-- The INSIGs perform distinct tasks in the regulation of these effectors- they promote ER retention of SCAP, but ubiquitin-mediated degradation of HMGR- Two questions that arise from the discovery and study of INSIGs are- how do they perform these distinct tasks, and how general are the actions of INSIGs in biology- We now show that the yeast INSIG homologs NSG1 and NSG2 function to control the stability of yeast Hmg2p, the HMGR isozyme that undergoes regulated ubiquitination- Yeast Nsgs inhibit degradation of Hmg2p in a highly specific manner, by directly interacting with the sterol-sensing domain -SSD--containing transmembrane region- Nsg1p functions naturally to limit degradation of Hmg2p when both proteins are at native levels, indicating a long-standing functional interplay between these two classes of proteins- One way to unify the known, disparate actions of INSIGs is to view them as known adaptations of a chaperone dedicated to SSD-containing client proteins-
[PUBMED: 16270032]