| First Author | Wei P | Year | 2012 |
| Journal | Mol Cell Biol | Volume | 32 |
| Issue | 2 | Pages | 266-75 |
| PubMed ID | 22064484 | Mgi Jnum | J:212788 |
| Mgi Id | MGI:5582154 | Doi | 10.1128/MCB.05674-11 |
| Citation | Wei P, et al. (2012) RNF34 is a cold-regulated E3 ubiquitin ligase for PGC-1alpha and modulates brown fat cell metabolism. Mol Cell Biol 32(2):266-75 |
| abstractText | The transcriptional coactivator PGC-1alpha is a master regulator of energy metabolism and adaptive thermogenesis in the brown fat cell. PGC-1alpha is a short-lived protein, and the molecular components that control PGC-1alpha turnover and their functional importance in energy metabolism are largely unknown. Here we performed a luciferase-based overexpression screen and identified a Ring-finger-containing protein, RNF34, as a specific E3 ubiquitin ligase for PGC-1alpha. RNF34 is a nuclear protein that interacts with and ubiquitinates PGC-1alpha to promote its turnover. Interestingly, RNF34 binds to the C-terminal half of PGC-1alpha and targets it for degradation independently of the previously identified N-terminal phosphodegron motif. In brown fat cells, knockdown of RNF34 increases the endogenous PGC-1alpha protein level, uncoupling protein 1 (UCP1) expression, and oxygen consumption, while the opposite effects are observed in brown fat cells ectopically expressing wild-type RNF34 but not in cells expressing the ligase activity-defective mutant. Moreover, cold exposure and beta3-adrenergic receptor signaling, conditions that induce PGC-1alpha expression, suppress RNF34 expression in the brown fat cell, indicating a physiological relevance of this E3 ligase in thermogenesis. Our results reveal that RNF34 is a bona fide E3 ubiquitin ligase for PGC-1alpha and negatively regulates brown fat cell metabolism. |
