Cyclin‐dependent kinases (CDKs), the master regulators of cell division, are activated by different cyclins at different cell cycle stages. In addition to being activators of CDKs, cyclins recognize various linear motifs to target CDK activity to specific proteins. We uncovered a cyclin docking motif, NLxxxL, that contributes to phosphorylation‐dependent degradation of the CDK inhibitor Far1 at the G1/S stage in the yeast Saccharomyces cerevisiae. This motif is recognized exclusively by S‐phase CDK (S‐CDK) Clb5/6‐Cdc28 and is considerably more potent than the conventional RxL docking motif. The NLxxxL and RxL motifs were found to overlap in some target proteins, suggesting that cyclin docking motifs can evolve to switch from one to another for fine‐tuning of cell cycle events. Using time‐lapse fluorescence microscopy, we show how different docking connections temporally control phosphorylation‐driven target degradation. This also revealed a differential function of the phosphoadaptor protein Cks1, as Cks1 docking potentiated degron phosphorylation of RxL‐containing but not of NLxxxL‐containing substrates. The NLxxxL motif was found to govern S‐cyclin‐specificity in multiple yeast CDK targets including Fin1, Lif1, and Slx4, suggesting its wider importance.

中文翻译：

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一个新的线性细胞周期蛋白对接基序，仅介导S期CDK特异性信号传导

细胞分裂的主要调节剂细胞周期蛋白依赖性激酶（CDKs）在不同的细胞周期阶段被不同的细胞周期蛋白激活。除了是CDK的激活剂外，细胞周期蛋白还识别各种线性基序，将CDK活性靶向特定蛋白质。我们发现了细胞周期蛋白对接基序NLxxxL，它有助于在酿酒酵母中G1 / S阶段CDK抑制剂Far1的磷酸化依赖性降解。。此基序仅由S相CDK（S-CDK）Clb5 / 6-Cdc28识别，并且比常规的RxL对接基序有效得多。发现NLxxxL和RxL基序在某些靶蛋白中重叠，这表明细胞周期蛋白对接基序可以进化为从一种切换到另一种，以进行细胞周期事件的微调。使用延时荧光显微镜，我们展示了不同的对接连接如何暂时控制磷酸化驱动的靶标降解。这也揭示了磷酸适体蛋白Cks1的差异功能，因为Cks1对接增强了含RxL而不是含NLxxxL的底物的degron磷酸化。发现NLxxxL基序可控制多个酵母CDK靶标（包括Fin1，Lif1和Slx4）中的S-cyclin特异性，表明其更重要的意义。