Document Detail

TRB3 links the E3 ubiquitin ligase COP1 to lipid metabolism.
MedLine Citation:
PMID:  16794074     Owner:  NLM     Status:  MEDLINE    
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 acid oxidation, these results demonstrate how phosphorylation and ubiquitination pathways converge on a key regulator of lipid metabolism to maintain energy homeostasis.
Ling Qi; Jose E Heredia; Judith Y Altarejos; Robert Screaton; Naomi Goebel; Sherry Niessen; Ian X Macleod; Chong Wee Liew; Rohit N Kulkarni; James Bain; Christopher Newgard; Michael Nelson; Ronald M Evans; John Yates; Marc Montminy
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Science (New York, N.Y.)     Volume:  312     ISSN:  1095-9203     ISO Abbreviation:  Science     Publication Date:  2006 Jun 
Date Detail:
Created Date:  2006-06-23     Completed Date:  2006-07-17     Revised Date:  2007-11-14    
Medline Journal Info:
Nlm Unique ID:  0404511     Medline TA:  Science     Country:  United States    
Other Details:
Languages:  eng     Pagination:  1763-6     Citation Subset:  IM    
Peptide Biology Laboratories and Gene Expression Laboratories, Salk Institute for Biological Studies, La Jolla, CA 92037, USA.
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MeSH Terms
3T3-L1 Cells
Acetyl-CoA Carboxylase / antagonists & inhibitors,  metabolism*
Adipocytes / metabolism
Adipose Tissue / cytology,  metabolism*
Adipose Tissue, Brown / cytology,  metabolism
Cell Cycle Proteins / metabolism*
Cell Line
Dietary Fats / administration & dosage
Energy Metabolism
Fatty Acids / metabolism
Gene Expression
Lipid Metabolism*
Mice, Transgenic
Nuclear Proteins / metabolism*
Obesity / prevention & control
Ubiquitin / metabolism
Ubiquitin-Protein Ligases / metabolism*
Weight Gain
Grant Support
Reg. No./Substance:
0/Cell Cycle Proteins; 0/Dietary Fats; 0/Fatty Acids; 0/Nuclear Proteins; 0/Rfwd2 protein, mouse; 0/TRB3 protein, mouse; 0/Ubiquitin; EC Ligases; EC Carboxylase
Comment In:
Science. 2006 Jun 23;312(5781):1756-8   [PMID:  16794069 ]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine

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