TRB3 links the E3 ubiquitin ligase COP1 to lipid metabolism.

Publisher: American Association for the Advancement of Science Country of Publication: United States NLM ID: 0404511 Publication Model: Print Cited Medium: Internet ISSN: 1095-9203 (Electronic) Linking ISSN: 00368075 NLM ISO Abbreviation: Science Subsets: MEDLINE

Publication: : Washington, DC : American Association for the Advancement of Science
Original Publication: New York, N.Y. : [s.n.] 1880-

Lipid Metabolism*; Acetyl-CoA Carboxylase/*metabolism ; Adipose Tissue/*metabolism ; Cell Cycle Proteins/*metabolism ; Nuclear Proteins/*metabolism ; Ubiquitin-Protein Ligases/*metabolism; 3T3-L1 Cells ; Acetyl-CoA Carboxylase/antagonists & inhibitors ; Adipocytes/metabolism ; Adipose Tissue/cytology ; Adipose Tissue, Brown/cytology ; Adipose Tissue, Brown/metabolism ; Animals ; Cell Line ; Dietary Fats/administration & dosage ; Energy Metabolism ; Fasting ; Fatty Acids/metabolism ; Gene Expression ; Humans ; Lipolysis ; Mice ; Mice, Transgenic ; Obesity/prevention & control ; Oxidation-Reduction ; Phosphorylation ; Thinness ; Ubiquitin/metabolism ; Weight Gain

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.

Comment in: Science. 2006 Jun 23;312(5781):1756-8. doi: 10.1126/science.1130476. (PMID: 16794069)

DK064142 United States DK NIDDK NIH HHS

0 (Cell Cycle Proteins)
0 (Dietary Fats)
0 (Fatty Acids)
0 (Nuclear Proteins)
0 (TRB3 protein, mouse)
0 (Ubiquitin)
EC 2.3.2.27 (COP1 protein, mouse)
EC 2.3.2.27 (Ubiquitin-Protein Ligases)
EC 6.4.1.2 (Acetyl-CoA Carboxylase)

Date Created: 20060624 Date Completed: 20060717 Latest Revision: 20240109

20250114

10.1126/science.1123374

16794074