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Identification of Cyclin-dependent Kinase 1 Specific Phosphorylation Sites by an In Vitro Kinase Assay
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Phosphatase specificity influences phosphorylation timing of CDK substrates during the cell cycle

Theresa U Zeisner1,2, Tania Auchynnikava3,4, Emma L Roberts3

  • 1Cell Cycle Laboratory, The Francis Crick Institute, London, UK. theresa.zeisner@imp.ac.at.

Nature Communications
|November 25, 2025
PubMed

Insights

Four phosphatases (PP2A-B55, PP2A-B56, CDC14, and PP1) control the timing of cyclin-dependent kinase (CDK) substrate phosphorylation during the cell cycle in fission yeast. Their specific targeting ensures proper regulation of cell cycle events.

Area of Science:

  • Cell Biology
  • Molecular Biology
  • Biochemistry

Background:

  • Cell cycle progression is regulated by cyclin-dependent kinases (CDKs) that phosphorylate numerous substrates.
  • The opposing roles of phosphatases in regulating CDK substrate phosphorylation in vivo are not fully understood.

Purpose of the Study:

  • To investigate the in vivo substrate specificity of four key phosphatases (PP2A-B55, PP2A-B56, CDC14, and PP1) in fission yeast.
  • To determine how these phosphatases collectively regulate the timing of CDK substrate phosphorylation during the G2 and M phases of the cell cycle.

Main Methods:

  • Utilized fission yeast as a model organism.
  • Investigated the substrate specificity of PP2A-B55, PP2A-B56, CDC14, and PP1 in vivo.
  • Analyzed the impact of phosphatase depletion on cell cycle progression and mitotic onset.

Main Results:

  • Each of the four phosphatases targets distinct subsets of CDK substrate sites.
  • The timing of site dephosphorylation by CDC14 and PP2A-B56 precedes that of PP1 and PP2A-B55.
  • Depletion of PP2A-B55 or CDC14 accelerates mitotic onset, indicating their role in regulating the G2/M transition.

Conclusions:

  • Phosphatase substrate specificity is crucial for setting phosphorylation thresholds at the G2/M transition.
  • These phosphatases play a key role in regulating the precise timing of CDK substrate phosphorylation throughout the cell cycle.
  • The findings highlight the importance of phosphatase activity in ordered cell cycle progression.

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