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FoxO1a-Cyclic GMP-Dependent Kinase I Interactions Orchestrate Myoblast Fusion

机译:FoxO1a循环GMP依赖激酶I相互作用协调成肌细胞融合。

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The regulatory circuits that orchestrate mammalian myoblast cell fusion during myogenesis are poorly understood. The transcriptional activity of FoxO1a directly regulates this process, yet the molecular mechanisms governing FoxO1a activity during muscle cell differentiation remain unknown. Here we show an autoregulatory loop in which FoxO1a directly activates transcription of the cyclic GMP-dependent protein kinase I (cGKI) gene and where the ensuing cGKI activity phosphorylates FoxO1a and abolishes its DNA binding activity. These findings establish the FoxO1a-to-cGKI pathway as a novel feedback loop that allows the precise tuning of myoblast fusion. Interestingly, this pathway appears to operate independently of muscle cell differentiation programs directed by myogenic transcription factors.
机译:人们很少了解在成肌过程中编排哺乳动物成肌细胞融合的调控电路。 FoxO1a的转录活性直接调节这一过程,但在肌肉细胞分化过程中控制FoxO1a活性的分子机制仍然未知。在这里,我们显示了一个自动调节环,其中FoxO1a直接激活依赖环GMP的蛋白激酶I( cGKI )基因的转录,随后产生的cGKI活性使FoxO1a磷酸化并消除其DNA结合活性。这些发现将FoxO1a到cGKI的途径确立为一种新颖的反馈回路,可以精确调节成肌细胞融合。有趣的是,该途径似乎独立于成肌转录因子指导的肌肉细胞分化程序而起作用。

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