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TRB3 Links the E3 Ubiquitin Ligase COPI to Lipid Metabolism.

Authors :
Ling Qi
Heredia, Jose E.
Altarejos, Judith Y.
Screaton, Robert
Goebel, Naomi
Niessen, Sherry
MacLeod, Ian X.
Chong Wee Liew
Kulkarni, Rohit N.
Bain, James
Newgard, Christopher
Nelson, Michael
Evans, Ronald M.
Yates, John
Montminy, Marc
Source :
Science. 6/23/2006, Vol. 312 Issue 5781, p1763-1766. 4p. 4 Diagrams.
Publication Year :
2006

Abstract

During fasting, increased concentrations of circulating catecholamines promote the mobilization of Lipid stores from adipose tissue in part by phosphorylating and inactivating acetyl-coenzyme A carboxylase (ACC), the rate-limiting enzyme in fatty acid synthesis. Here, we describe a parallel pathway, in which the pseudokinase TribbLes 3 (TRB3), whose abundance is increased during fasting, stimulates lipolysis by triggering the degradation of ACC in adipose tissue. TRB3 promoted ACC ubiquitination through an association with the E3 ubiquitin ligase constitutive photomorphogenic protein 1 (COP1). Indeed, adipocytes deficient in TRB3 accumulated larger amounts of ACC protein than did wild-type cells. Because transgenic mice expressing TRB3 in adipose tissue are protected from diet-induced obesity due to enhanced fatty add oxidation, these results demonstrate how phosphorylation and ubiquitination pathways converge on a key regulator of lipid metabolism to maintain energy homeostasis. [ABSTRACT FROM AUTHOR]

Details

Language :
English
ISSN :
00368075
Volume :
312
Issue :
5781
Database :
Academic Search Index
Journal :
Science
Publication Type :
Academic Journal
Accession number :
21507265