Biochemical analyses reveal amino acid residues critical for cell cycle-dependent phosphorylation of human Cdc14A phosphatase by cyclin-dependent kinase 1

Sci Rep. 2018 Aug 8;8(1):11871. doi: 10.1038/s41598-018-30253-8.

Abstract

Cdc14 enzymes compose a family of highly conserved phosphatases that are present in a wide range of organisms, including yeast and humans, and that preferentially reverse the phosphorylation of Cyclin-Dependent Kinase (Cdk) substrates. The budding yeast Cdc14 orthologue has essential functions in the control of late mitosis and cytokinesis. In mammals, however, the two Cdc14 homologues, Cdc14A and Cdc14B, do not play a prominent role in controlling late mitotic events, suggesting that some Cdc14 functions are not conserved across species. Moreover, in yeast, Cdc14 is regulated by changes in its subcellular location and by phosphorylation events. In contrast, little is known about the regulation of human Cdc14 phosphatases. Here, we have studied how the human Cdc14A orthologue is regulated during the cell cycle. We found that Cdc14A is phosphorylated on Ser411, Ser453 and Ser549 by Cdk1 early in mitosis and becomes dephosphorylated during late mitotic stages. Interestingly, in vivo and in vitro experiments revealed that, unlike in yeast, Cdk1-mediated phosphorylation of human Cdc14A did not control its catalytic activity but likely modulated its interaction with other proteins in early mitosis. These findings point to differences in Cdk1-mediated mechanisms of regulation between human and yeast Cdc14 orthologues.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acids / metabolism*
  • Biochemical Phenomena / physiology
  • CDC2 Protein Kinase / metabolism*
  • Cell Cycle / physiology*
  • Cell Cycle Proteins / metabolism
  • Cell Line
  • Cell Line, Tumor
  • Cytokinesis / physiology
  • Fungal Proteins / metabolism
  • HEK293 Cells
  • HeLa Cells
  • Humans
  • Mitosis / physiology
  • Phosphoric Monoester Hydrolases / metabolism*
  • Phosphorylation / physiology*
  • Yeasts / metabolism

Substances

  • Amino Acids
  • Cell Cycle Proteins
  • Fungal Proteins
  • CDC2 Protein Kinase
  • CDK1 protein, human
  • Phosphoric Monoester Hydrolases
  • CDC14A protein, human