| First Author | Fan M | Year | 2004 |
| Journal | Genes Dev | Volume | 18 |
| Issue | 3 | Pages | 278-89 |
| PubMed ID | 14744933 | Mgi Jnum | J:88279 |
| Mgi Id | MGI:3032469 | Doi | 10.1101/gad.1152204 |
| Citation | Fan M, et al. (2004) Suppression of mitochondrial respiration through recruitment of p160 myb binding protein to PGC-1alpha: modulation by p38 MAPK. Genes Dev 18(3):278-89 |
| abstractText | The transcriptional coactivator PPAR gamma coactivator 1 alpha (PGC-1alpha) is a key regulator of metabolic processes such as mitochondrial biogenesis and respiration in muscle and gluconeogenesis in liver. Reduced levels of PGC-1alpha in humans have been associated with type II diabetes. PGC-1alpha contains a negative regulatory domain that attenuates its transcriptional activity. This negative regulation is removed by phosphorylation of PGC-1alpha by p38 MAPK, an important kinase downstream of cytokine signaling in muscle and beta-adrenergic signaling in brown fat. We describe here the identification of p160 myb binding protein (p160MBP) as a repressor of PGC-1alpha. The binding and repression of PGC-1alpha by p160MBP is disrupted by p38 MAPK phosphorylation of PGC-1alpha. Adenoviral expression of p160MBP in myoblasts strongly reduces PGC-1alpha's ability to stimulate mitochondrial respiration and the expression of the genes of the electron transport system. This repression does not require removal of PGC-1alpha from chromatin, suggesting that p160MBP is or recruits a direct transcriptional suppressor. Overall, these data indicate that p160MBP is a powerful negative regulator of PGC-1alpha function and provide a molecular mechanism for the activation of PGC-1alpha by p38 MAPK. The discovery of p160MBP as a PGC-1alpha regulator has important implications for the understanding of energy balance and diabetes. |
