Cyclin A and Cks1 promote kinase consensus switching to non-proline-directed CDK1 phosphorylation

Aymen al-Rawi, Edward Kaye, Svitlana Korolchuk, Jane A. Endicott, Tony Ly*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

Abstract / Description of output

Ordered protein phosphorylation by CDKs is a key mechanism for regulating the cell cycle. How temporal order is enforced in mammalian cells remains unclear. Using a fixed cell kinase assay and phosphoproteomics, we show how CDK1 activity and non-catalytic CDK1 subunits contribute to the choice of substrate and site of phosphorylation. Increases in CDK1 activity alter substrate choice, with intermediate- and low-sensitivity CDK1 substrates enriched in DNA replication and mitotic functions, respectively. This activity dependence is shared between Cyclin A- and Cyclin B-CDK1. Cks1 has a proteome-wide role as an enhancer of multisite CDK1 phosphorylation. Contrary to the model of CDK1 as an exclusively proline-directed kinase, we show that Cyclin A and Cks1 enhance non-proline-directed phosphorylation, preferably on sites with a +3 lysine residue. Indeed, 70% of cell-cycle-regulated phosphorylations, where the kinase carrying out this modification has not been identified, are non-proline-directed CDK1 sites.

Original languageEnglish
Article number112139
Pages (from-to)112139
Number of pages20
JournalCell Reports
Volume42
Issue number3
Early online date24 Feb 2023
DOIs
Publication statusPublished - 28 Mar 2023

Keywords / Materials (for Non-textual outputs)

  • cell cycle
  • CP: Cell biology
  • CP: Molecular biology
  • kinase consensus motif
  • mitosis
  • phosphoproteomics

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