Cell proliferation exerts a high demand on protein synthesis, yet the mechanisms coupling the two processes are not fully understood. A kinase and phosphatase screen for activators of translation, based on the formation of stress granules in human cells, revealed cell cycle–associated kinases as major candidates. CDK1 was identified as a positive regulator of global translation, and cell synchronization experiments showed that this is an extramitotic function of CDK1. Different pathways including eIF2α, 4EBP, and S6K1 signaling contribute to controlling global translation downstream of CDK1. Moreover, Ribo-Seq analysis uncovered that CDK1 exerts a particularly strong effect on the translation of 5′TOP mRNAs, which includes mRNAs encoding ribosomal proteins and several translation factors. This effect requires the 5′TOP mRNA-binding protein LARP1, concurrent to our finding that LARP1 phosphorylation is strongly dependent on CDK1. Thus, CDK1 provides a direct means to couple cell proliferation with biosynthesis of the translation machinery and the rate of protein synthesis.

中文翻译：

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CDK1 将增殖与蛋白质合成结合起来


细胞增殖对蛋白质合成提出了很高的要求，然而这两个过程的耦合机制尚不完全清楚。基于人类细胞中应激颗粒的形成，对翻译激活剂进行激酶和磷酸酶筛选，结果显示细胞周期相关激酶是主要候选者。 CDK1被确定为全局翻译的正调节因子，细胞同步实验表明这是CDK1的有丝分裂外功能。包括 eIF2α、4EBP 和 S6K1 信号传导在内的不同途径有助于控制 CDK1 下游的全局翻译。此外，Ribo-Seq 分析发现 CDK1 对 5'TOP mRNA 的翻译具有特别强烈的影响，其中包括编码核糖体蛋白和多种翻译因子的 mRNA。这种效应需要 5'TOP mRNA 结合蛋白 LARP1，同时我们发现 LARP1 磷酸化强烈依赖于 CDK1。因此，CDK1 提供了一种将细胞增殖与翻译机制的生物合成和蛋白质合成速率耦合的直接方法。