Proline-Rich Motifs Control G2-CDK Target Phosphorylation and Priming an Anchoring Protein for Polo Kinase Localization

• DOI: 10.1016/j.celrep.2020.107757
• Publication Date: 2020-06-16T14:34:05Z
• Authors: Mihkel Örd; Kait Kaarel Puss; Rait Kivi; Kaidi Möll; Tuuliki Ojala; Irina Borovko; Ilona Faustova; Rainis Venta; Ervin Valk; Mardo Kõivomägi; Mart Loog
• Keywords: 0301 basic medicine; Saccharomyces cerevisiae Proteins; Proline; QH301-705.5; Cell Cycle; Cell Cycle Proteins; Cell Cycle Checkpoints; Saccharomyces cerevisiae; short linear motif; Article; Cyclin-Dependent Kinases; Substrate Specificity; 03 medical and health sciences; cyclin-dependent kinase; kinase specificity; Polo kinase; Humans; cell cycle; Biology (General); Phosphorylation; SLiM

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.