You are hereRecent Publications of Members of the Boston Ithaca Islet Club / TRB3 links the E3 ubiquitin ligase COP1 to lipid metabolism
TRB3 links the E3 ubiquitin ligase COP1 to lipid metabolism
| Title | TRB3 links the E3 ubiquitin ligase COP1 to lipid metabolism |
| Publication Type | Journal Article |
| Year of Publication | 2006 |
| Authors | |
| Journal | Science |
| Volume | 312 |
| Issue | 5781 |
| Pagination | 1763-6 |
| Date Published | Jun 23 |
| Publication Language | eng |
| ISBN Number | 1095-9203 (Electronic) |
| Accession Number | 16794074 |
| Key Words | Energy Metabolism, Dietary Fats/administration & dosage, Cell Line, Cell Cycle Proteins/*metabolism, Animals, Adipose Tissue, 3T3-L1 Cells, Weight Gain, Phosphorylation, Oxidation-Reduction, Mice, Transgenic, Lipolysis, *Lipid Metabolism, Humans, Gene Expression, Fatty Acids/metabolism, Fasting, Brown/cytology/metabolism, Adipose Tissue/cytology/*metabolism, Adipocytes/metabolism, Acetyl-CoA Carboxylase/antagonists & inhibitors/*metabolism, Ubiquitin-Protein Ligases/*metabolism, Ubiquitin/metabolism, Thinness, Obesity/prevention & control, Nuclear Proteins/*metabolism |
| 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 acid oxidation, these results demonstrate how phosphorylation and ubiquitination pathways converge on a key regulator of lipid metabolism to maintain energy homeostasis. |
| Notes | DK064142/DK/NIDDK NIH HHS/United StatesJournal ArticleResearch Support, N.I.H., ExtramuralResearch Support, Non-U.S. Gov'tUnited States |
| URL | http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=16794074 |
| Citation Key | 497 |
| Export |
- *Lipid Metabolism
- 3T3-L1 Cells
- Acetyl-CoA Carboxylase/antagonists & inhibitors/*metabolism
- Adipocytes/metabolism
- Adipose Tissue, Brown/cytology/metabolism
- Adipose Tissue/cytology/*metabolism
- Animals
- Cell Cycle Proteins/*metabolism
- Cell Line
- Dietary Fats/administration & dosage
- Energy Metabolism
- Fasting
- Fatty Acids/metabolism
- Gene Expression
- Humans
- Lipolysis
- Mice
- Mice, Transgenic
- Nuclear Proteins/*metabolism
- Obesity/prevention & control
- Oxidation-Reduction
- Phosphorylation
- Thinness
- Ubiquitin-Protein Ligases/*metabolism
- Ubiquitin/metabolism
- Weight Gain