Ringo/Cyclin-dependent Kinase and Mitogen-activated Protein Kinase Signaling Pathways Regulate the Activity of the Cell Fate Determinant Musashi to Promote Cell Cycle Re-entry in Xenopus Oocytes
Ringo/Cyclin-dependent Kinase and Mitogen-activated Protein Kinase Signaling Pathways Regulate the Activity of the Cell Fate Determinant Musashi to Promote Cell Cycle Re-entry in Xenopus Oocytes
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DOI：
10.1074/jbc.m111.300681
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发表时间：
2012-03-23
影响因子：
4.8
通讯作者：
MacNicol, Angus M.
中科院分区：
文献类型：
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作者：
Arumugam, Karthik;MacNicol, Melanie C.;MacNicol, Angus M.
脊椎动物卵母细胞成熟期间的细胞周期重新进入是通过选定靶mRNA的翻译激活介导的，最终激活有丝分裂原活化蛋白激酶和细胞周期蛋白B/细胞周期蛋白依赖性激酶（CDK）信号传导。靶向mRNA翻译的时间顺序对于细胞周期进展至关重要，并且由不同mRNA结合蛋白的激活时间决定。我们以前已经表明，在卵母细胞从非洲爪蟾的mRNA结合蛋白武藏的目标翻译激活的早期类mRNA，包括mRNA编码的莫斯原癌基因。然而，武藏功能被激活的分子机制尚不清楚。我们在这里报告，Musashi 1的激活是由Ringo/CDK信号转导介导的，揭示了早期Ringo/CDK功能的新作用。有趣的是，Musashi 1的激活随后通过有丝分裂原活化蛋白激酶信号传导（Mos mRNA翻译的下游效应子）持续，从而建立了一个正反馈环来放大Musashi功能。所确定的调控位点存在于哺乳动物Musashi蛋白中，我们的数据表明磷酸化可能代表了一种进化上保守的机制来控制Musashi依赖的靶mRNA翻译。
Cell cycle re-entry during vertebrate oocyte maturation is mediated through translational activation of select target mRNAs, culminating in the activation of mitogen-activated protein kinase and cyclin B/cyclin-dependent kinase (CDK) signaling. The temporal order of targeted mRNA translation is crucial for cell cycle progression and is determined by the timing of activation of distinct mRNA-binding proteins. We have previously shown in oocytes from Xenopus laevis that the mRNA-binding protein Musashi targets translational activation of early class mRNAs including the mRNA encoding the Mos proto-oncogene. However, the molecular mechanism by which Musashi function is activated is unknown. We report here that activation of Musashi1 is mediated by Ringo/CDK signaling, revealing a novel role for early Ringo/CDK function. Interestingly, Musashi1 activation is subsequently sustained through mitogen-activated protein kinase signaling, the downstream effector of Mos mRNA translation, thus establishing a positive feedback loop to amplify Musashi function. The identified regulatory sites are present in mammalian Musashi proteins, and our data suggest that phosphorylation may represent an evolutionarily conserved mechanism to control Musashi-dependent target mRNA translation.