Cdc14 and PP2A Phosphatases Cooperate to Shape Phosphoproteome Dynamics during Mitotic Exit

Cell Rep. 2019 Nov 12;29(7):2105-2119.e4. doi: 10.1016/j.celrep.2019.10.041.


Temporal control over protein phosphorylation and dephosphorylation is crucial for accurate chromosome segregation and for completion of the cell division cycle during exit from mitosis. In budding yeast, the Cdc14 phosphatase is thought to be a major regulator at this time, while in higher eukaryotes PP2A phosphatases take a dominant role. Here, we use time-resolved phosphoproteome analysis in budding yeast to evaluate the respective contributions of Cdc14, PP2ACdc55, and PP2ARts1. This reveals an overlapping requirement for all three phosphatases during mitotic progression. Our time-resolved phosphoproteome resource reveals how Cdc14 instructs the sequential pattern of phosphorylation changes, in part through preferential recognition of serine-based cyclin-dependent kinase (Cdk) substrates. PP2ACdc55 and PP2ARts1 in turn exhibit a broad substrate spectrum with some selectivity for phosphothreonines and a role for PP2ARts1 in sustaining Aurora kinase activity. These results illustrate synergy and coordination between phosphatases as they orchestrate phosphoproteome dynamics during mitotic progression.

Keywords: Cdc14; PP2A; cell cycle; mitotic exit; phosphatases; phosphoproteomics.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cell Cycle Proteins / genetics
  • Cell Cycle Proteins / metabolism*
  • Mitosis*
  • Phosphoproteins / genetics
  • Phosphoproteins / metabolism*
  • Protein Phosphatase 2 / genetics
  • Protein Phosphatase 2 / metabolism*
  • Protein Tyrosine Phosphatases / genetics
  • Protein Tyrosine Phosphatases / metabolism*
  • Proteome / genetics
  • Proteome / metabolism*
  • Saccharomyces cerevisiae / genetics
  • Saccharomyces cerevisiae / metabolism*
  • Saccharomyces cerevisiae Proteins / genetics
  • Saccharomyces cerevisiae Proteins / metabolism*


  • CDC14 protein, S cerevisiae
  • CDC55 protein, S cerevisiae
  • Cell Cycle Proteins
  • Phosphoproteins
  • Proteome
  • Saccharomyces cerevisiae Proteins
  • Protein Phosphatase 2
  • Rts1 protein, S cerevisiae
  • Protein Tyrosine Phosphatases