SIK1 is a class II HDAC kinase that promotes survival of skeletal myocytes
Copyright policy )SIK1 is a class II HDAC kinase that promotes survival of skeletal myocytes
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.
- University of California, San Diego United States
- Stanford University United States
- Salk Institute for Biological Studies United States
- Osaka University Japan
- University of California, San Diego United States
Motor Neurons, Muscle Cells, Cell Survival, MEF2 Transcription Factors, Histone Deacetylase 2, Mice, Transgenic, Muscular Dystrophy, Animal, Protein Serine-Threonine Kinases, Histone Deacetylases, Repressor Proteins, Mice, Gene Expression Regulation, Myogenic Regulatory Factors, Animals, Humans, Calcium, Cyclic AMP Response Element-Binding Protein, Muscle, Skeletal, Exercise
Motor Neurons, Muscle Cells, Cell Survival, MEF2 Transcription Factors, Histone Deacetylase 2, Mice, Transgenic, Muscular Dystrophy, Animal, Protein Serine-Threonine Kinases, Histone Deacetylases, Repressor Proteins, Mice, Gene Expression Regulation, Myogenic Regulatory Factors, Animals, Humans, Calcium, Cyclic AMP Response Element-Binding Protein, Muscle, Skeletal, Exercise
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