Proline-Rich Motifs Control G2-CDK Target Phosphorylation and Priming an Anchoring Protein for Polo Kinase Localization
Proline-Rich Motifs Control G2-CDK Target Phosphorylation and Priming an Anchoring Protein for Polo Kinase Localization
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DOI：
10.1016/j.celrep.2020.107757
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发表时间：
2020-06-16
期刊：
影响因子：
8.8
通讯作者：
Loog, Mart
中科院分区：
文献类型：
--
作者：
Ord, Mihkel;Puss, Kait Kaarel;Loog, Mart
疏水补丁(Hp)是CDK(细胞周期蛋白依赖性激酶)周期蛋白上的一个对接口袋，被认为容纳了一个单一的短线性基序(SLIM)，即“RXL或Cy”对接基序。在这里，我们证明了hp可以高度特异性地结合不同的基序。我们鉴定了酿酒酵母中G2-细胞周期蛋白Clb3功能所必需的PxxPxF基序，并介导Ypr174c的Clb3-CDK1磷酸化(建议命名：CDC5 SPB锚-Csa1)来调节Polo激酶CDC5的定位。类似的基序也存在于其他Clb3-CDK1靶标中。我们的工作完成了四种主要细胞周期蛋白的对接特异性：分别针对G1期、S期、G2期和M期细胞周期蛋白的Lp、RxL、PxxPxF和Lxf基序。此外，我们还表明，基序的变化可以改变其对人类周期蛋白的特异性。这种多样性为CDK阈值的编码提供了复杂性，从而实现了细胞周期有序的磷酸化。
The hydrophobic patch (hp), a docking pocket on cyclins of CDKs (cyclin-dependent kinases), has been thought to accommodate a single short linear motif (SLiM), the "RxL or Cy" docking motif. Here we show that hp can bind different motifs with high specificity. We identify a PxxPxF motif that is necessary for G2-cyclin Clb3 function in S. cerevisiae, and that mediates Clb3-Cdk1 phosphorylation of Ypr174c (proposed name: Cdc5 SPB anchor-Csa1) to regulate the localization of Polo kinase Cdc5. Similar motifs exist in other Clb3-Cdk1 targets. Our work completes the set of docking specificities for the four major cyclins: LP, RxL, PxxPxF, and LxF motifs for G1-, S-, G2-, and M-phase cyclins, respectively. Further, we show that variations in motifs can change their specificity for human cyclins. This diversity could provide complexity for the encoding of CDK thresholds to achieve ordered cell-cycle phosphorylation.