Skeletal muscle atrophy is caused by a decrease in muscle size and strength and results from a range of physiological conditions, including denervation, immobilization, corticosteroid exposure and aging. Newly named dual-specificity phosphatase 29 (Dusp29) has been identified as a novel neurogenic atrophy-induced gene in skeletal muscle. Quantitative PCR analysis revealed that Dusp29 expression is significantly higher in differentiated myotubes compared with proliferating myoblasts. To determine how Dusp29 is transcriptionally regulated in skeletal muscle, fragments of the promoter region of Dusp29 were cloned, fused to a reporter gene, and found to be highly inducible in response to ectopic expression of the myogenic regulatory factors (MRF), MyoD and myogenin. Furthermore, site-directed mutagenesis of conserved E-box elements within the proximal promoter of Dusp29 rendered a Dusp29 reporter gene unresponsive to MRF overexpression. Dusp29, an atypical Dusp also known as Dupd1/Dusp27, was found to attenuate the ERK1/2 branch of the MAP kinase signaling pathway in muscle cells and inhibit muscle cell differentiation when ectopically expressed in proliferating myoblasts. Interestingly, Dusp29 was also found to destabilize AMPK protein while simultaneously enriching the phosphorylated pool of AMPK in muscle cells. Additionally, Dusp29 overexpression resulted in a significant increase in the glucocorticoid receptor (GR) protein and elevation in GR phosphorylation. Finally, Dusp29 was found to significantly impair the ability of the glucocorticoid receptor to function as a transcriptional activator in muscle cells treated with dexamethasone. Identifying and characterizing the function of Dusp29 in muscle provides novel insights into the molecular and cellular mechanisms for skeletal muscle atrophy.

中文翻译：

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在神经源性骨骼肌萎缩期间诱导双重特异性磷酸酶29，并减弱肌肉细胞培养物中糖皮质激素受体的活性。

骨骼肌萎缩是由肌肉大小和强度的下降引起的，并且是由一系列生理条件（包括神经支配，固定，皮质类固醇暴露和衰老）导致的。新命名的双特异性磷酸酶29（Dusp29）已被确定为骨骼肌中一种新型的神经性萎缩诱导基因。定量PCR分析显示，与增殖的成肌细胞相比，Dusp29在分化的肌管中的表达明显更高。为了确定Dusp29在骨骼肌中是如何转录调控的，Dusp29启动子区域的片段将其克隆，融合到报告基因上，并发现其对肌源性调节因子（MRF），MyoD和肌生成素的异位表达具有高度诱导性。此外，在Dusp29的近端启动子内保守的E-box元件的定点诱变提供了Dusp29报告基因对MRF过表达无反应。发现Dusp29是一种非典型的Dusp，也称为Dupd1 / Dusp27，当在成肌成肌细胞中异位表达时，它会减弱肌肉细胞中MAP激酶信号传导途径的ERK1 / 2分支并抑制肌肉细胞分化。有趣的是，还发现Dusp29使AMPK蛋白不稳定，同时在肌肉细胞中富集了AMPK的磷酸化库。此外，Dusp29过表达导致糖皮质激素受体（GR）蛋白显着增加，并且GR磷酸化升高。最后，发现Dusp29大大削弱了糖皮质激素受体在地塞米松处理的肌肉细胞中作为转录激活因子的功能。