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

Cell Rep. 2020 Jun 16;31(11):107757. doi: 10.1016/j.celrep.2020.107757.

Abstract

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.

Keywords: Polo kinase; SLiM; cell cycle; cyclin-dependent kinase; intrinsically disordered regions; kinase specificity; short linear motif.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cell Cycle / physiology
  • Cell Cycle Checkpoints / physiology*
  • Cell Cycle Proteins / metabolism*
  • Cyclin-Dependent Kinases / metabolism*
  • Humans
  • Phosphorylation
  • Proline / metabolism*
  • Saccharomyces cerevisiae / metabolism
  • Saccharomyces cerevisiae Proteins / metabolism
  • Substrate Specificity / physiology

Substances

  • Cell Cycle Proteins
  • Saccharomyces cerevisiae Proteins
  • Proline
  • Cyclin-Dependent Kinases