SIK1 is a class II HDAC kinase that promotes survival of skeletal myocytes

Rebecca Berdeaux, Naomi Goebel, Laura Banaszynski, Hiroshi Takemori, Thomas Wandless, G. Diane Shelton, Marc Montminy

Research output: Contribution to journalArticlepeer-review

216 Scopus citations


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.

Original languageEnglish (US)
Pages (from-to)597-603
Number of pages7
JournalNature medicine
Issue number5
StatePublished - May 2007

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)


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