细胞生物学
心肌细胞
癌症研究
组蛋白脱乙酰基酶
化学
C2C12型
细胞生长
细胞凋亡
蛋白激酶B
肌发生
基因敲除
作者
Rebecca Berdeaux,Naomi Goebel,Laura A. Banaszynski,Hiroshi Takemori,Thomas J. Wandless,G. Diane Shelton,Marc Montminy
出处
期刊:Nature Medicine
[Springer Nature]
日期:2007-04-29
卷期号:13 (5): 597-603
被引量:241
摘要
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.
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