@article{3a4c9c01ee464acbac1de602916ed225,
title = "Yeast SREBP Cleavage Activation Requires the Golgi Dsc E3 Ligase Complex",
abstract = "Mammalian lipid homeostasis requires proteolytic activation of membrane-bound sterol regulatory element binding protein (SREBP) transcription factors through sequential action of the Golgi Site-1 and Site-2 proteases. Here we report that while SREBP function is conserved in fungi, fission yeast employs a different mechanism for SREBP cleavage. Using genetics and biochemistry, we identified four genes defective for SREBP cleavage, dsc1-4, encoding components of a transmembrane Golgi E3 ligase complex with structural homology to the Hrd1 E3 ligase complex involved in endoplasmic reticulum-associated degradation. The Dsc complex binds SREBP and cleavage requires components of the ubiquitin-proteasome pathway: the E2-conjugating enzyme Ubc4, the Dsc1 RING E3 ligase, and the proteasome. dsc mutants display conserved aggravating genetic interactions with components of the multivesicular body pathway in fission yeast and budding yeast, which lacks SREBP. Together, these data suggest that the Golgi Dsc E3 ligase complex functions in a post-ER pathway for protein degradation.",
author = "Stewart, {Emerson V.} and Nwosu, {Christine C.} and Zongtian Tong and Assen Roguev and Cummins, {Timothy D.} and Kim, {Dong Uk} and Jacqueline Hayles and Park, {Han Oh} and Hoe, {Kwang Lae} and Powell, {David W.} and Krogan, {Nevan J.} and Espenshade, {Peter J.}",
note = "Funding Information: This work was supported by grants from the National Institutes of Health HL077588 (P.J.E.), GM084279 (N.J.K.), DK176743 (D.W.P.); the Searle Foundation (N.J.K.); and the Keck Foundation (N.J.K.). P.J.E. is an Established Investigator of the American Heart Association; C.C.N. is an Isaac Morris Hay and Lucille Elizabeth Hay Graduate Fellow. We thank M. Shales for technical assistance and members of the Espenshade lab, J. Burg for computational assistance, S. Zhao for technical assistance, and A. Hughes and B. Hughes for preliminary experiments. We are grateful to these investigators for sharing strains and plasmids: Shelley Sazer (Baylor College of Medicine), Snezhana Oliferenko (TLL, Singapore), Hiroaki Seino (Osaka City University, Japan), Ben Glick (University of Chicago), Colin Gordon (Medical Research Council, UK), and Kaoru Takegawa (Kagawa University, Japan). ",
year = "2011",
month = apr,
day = "22",
doi = "10.1016/j.molcel.2011.02.035",
language = "English",
volume = "42",
pages = "160--171",
journal = "Molecular Cell",
issn = "1097-2765",
publisher = "Cell Press",
number = "2",
}