| First Author | Berdeaux R | Year | 2007 |
| Journal | Nat Med | Volume | 13 |
| Issue | 5 | Pages | 597-603 |
| PubMed ID | 17468767 | Mgi Jnum | J:121892 |
| Mgi Id | MGI:3712602 | Doi | 10.1038/nm1573 |
| Citation | Berdeaux R, et al. (2007) SIK1 is a class II HDAC kinase that promotes survival of skeletal myocytes. Nat Med 13(5):597-603 |
| abstractText | During physical exercise, increases in motor neuron activity stimulate the expression of muscle-specific genes through the myocyte enhancer factor 2 (MEF2) family of transcription factors. Elevations in intracellular calcium increase MEF2 activity via the phosphorylation-dependent inactivation of class II histone deacetylases (HDACs). In studies to determine the role of the cAMP responsive element binding protein (CREB) in skeletal muscle, we found that mice expressing a dominant-negative CREB transgene (M-ACREB mice) exhibited a dystrophic phenotype along with reduced MEF2 activity. Class II HDAC phosphorylation was decreased in M-ACREB myofibers due to a reduction in amounts of Snf1lk (encoding salt inducible kinase, SIK1), a CREB target gene that functions as a class II HDAC kinase. Inhibiting class II HDAC activity either by viral expression of Snf1lk or by the administration of a small molecule antagonist improved the dystrophic phenotype in M-ACREB mice, pointing to an important role for the SIK1-HDAC pathway in regulating muscle function. |
