Functional homology among human and fission yeast Cdc14 phosphatases.
Budding and fission yeast Cdc14 homologues, a conserved family of serine-threonine phosphatases, play a role in the inactivation of mitotic cyclin-dependent kinases (CDKs) by molecularly distinct mechanisms. Saccharomyces cerevisiae Cdc14 protein phosphatase inactivates CDKs by promoting mitotic cyclin degradation and the accumulation of a CDK inhibitor to allow budding yeast cells to exit from mitosis. Schizosaccharomyces pombe Flp1 phosphatase down-regulates CDK/cyclin activity, controlling the degradation of the Cdc25 tyrosine phosphatase for fission yeast cells to undergo cytokinesis. In the present work, we show that human Cdc14 homologues (hCdc14A and hCdc14B) rescued flp1-deficient fission yeast strains, indicating functional homology. We also show that hCdc14A and B interacted in vivo with S. pombe Cdc25 and that hCdc14A dephosphorylated this mitotic inducer both in vitro and in vivo. Our results support a Cdc14 conserved inhibitory mechanism acting on S. pombe Cdc25 protein and suggest that human cells may regulate Cdc25 in a similar manner to inactivate Cdk1-mitotic cyclin complexes.
Vázquez-Novelle
M Dolores
MD
Centro de Investigación del Cáncer and Departamento de Microbiología y Genética, Campus Miguel de Unamuno, Universidad de Salamanca/Consejo Superior de Investigaciones Científicas, 37007 Salamanca, Spain.
Esteban
Verónica
V
Bueno
Avelino
A
Sacristán
María P
MP
D015153:Blotting, Western; D018797:Cell Cycle Proteins / Q000737:chemistry / Q000378:metabolism; D002467:Cell Nucleus / Q000378:metabolism; D048749:Cytokinesis; D004247:DNA / Q000737:chemistry; D015536:Down-Regulation; D005434:Flow Cytometry; D005816:Genetic Complementation Test; D005982:Glutathione Transferase / Q000378:metabolism; D006801:Humans; D047468:Immunoprecipitation; D008856:Microscopy, Fluorescence; D008938:Mitosis; D010641:Phenotype; D010749:Phosphoprotein Phosphatases / Q000737:chemistry*; D010744:Phosphoric Monoester Hydrolases / Q000737:chemistry*; D010766:Phosphorylation; D010957:Plasmids / Q000378:metabolism; D011485:Protein Binding; D017027:Protein Tyrosine Phosphatases / Q000737:chemistry / Q000378:metabolism; D011993:Recombinant Fusion Proteins / Q000378:metabolism; D029701:Saccharomyces cerevisiae Proteins / Q000737:chemistry*; D012568:Schizosaccharomyces / Q000201:enzymology*; D029702:Schizosaccharomyces pombe Proteins / Q000378:metabolism; D008941:Spindle Apparatus; D013696:Temperature
C074860:CDC14 protein, S cerevisiae; D018797:Cell Cycle Proteins; D011993:Recombinant Fusion Proteins; D029701:Saccharomyces cerevisiae Proteins; D029702:Schizosaccharomyces pombe Proteins; D004247:DNA; D005982:Glutathione Transferase; C503885:CDC14 protein, S pombe; D010749:Phosphoprotein Phosphatases; D010744:Phosphoric Monoester Hydrolases; C120902:CDC14A protein, human; C439269:Clp1 protein, S. pombe; D017027:Protein Tyrosine Phosphatases