Global analysis of cdc14 dephosphorylation sites reveals essential regulatory role in mitosis and cytokinesis

Mol Cell Proteomics. 2014 Feb;13(2):594-605. doi: 10.1074/mcp.M113.032680. Epub 2013 Dec 7.

Abstract

Degradation of the M phase cyclins triggers the exit from M phase. Cdc14 is the major phosphatase required for the exit from the M phase. One of the functions of Cdc14 is to dephosphorylate and activate the Cdh1/APC/C complex, resulting in the degradation of the M phase cyclins. However, other crucial targets of Cdc14 for mitosis and cytokinesis remain to be elucidated. Here we systematically analyzed the positions of dephosphorylation sites for Cdc14 in the budding yeast Saccharomyces cerevisiae. Quantitative mass spectrometry identified a total of 835 dephosphorylation sites on 455 potential Cdc14 substrates in vivo. We validated two events, and through functional studies we discovered that Cdc14-mediated dephosphorylation of Smc4 and Bud3 is essential for proper mitosis and cytokinesis, respectively. These results provide insight into the Cdc14-mediated pathways for exiting the M phase.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Binding Sites
  • Cell Cycle Proteins / metabolism*
  • Chromosomal Proteins, Non-Histone / metabolism
  • Chromosome Segregation
  • Cytokinesis* / genetics
  • DNA Packaging
  • Mitosis* / genetics
  • Phosphoproteins / chemistry
  • Phosphoproteins / metabolism*
  • Phosphorylation
  • Protein Processing, Post-Translational
  • Protein Tyrosine Phosphatases / metabolism*
  • Proteome / analysis
  • Proteome / metabolism
  • Saccharomyces cerevisiae / metabolism
  • Saccharomyces cerevisiae Proteins / chemistry
  • Saccharomyces cerevisiae Proteins / metabolism*
  • Tandem Mass Spectrometry

Substances

  • BUD3 protein, S cerevisiae
  • CDC14 protein, S cerevisiae
  • Cell Cycle Proteins
  • Chromosomal Proteins, Non-Histone
  • Phosphoproteins
  • Proteome
  • SMC4 protein, S cerevisiae
  • Saccharomyces cerevisiae Proteins
  • Protein Tyrosine Phosphatases