Fission yeast Clp1p phosphatase affects G2/M transition and mitotic exit through Cdc25p inactivation.
The Cdc14 family of phosphatases specifically reverses proline-directed phosphorylation events. In Saccharomyces cerevisiae, Cdc14p promotes Cdk1p inactivation at mitotic exit by reversing Cdk1p-dependent phosphorylations. Cdk1p is a proline-directed kinase whose activity is required in all eukaryotes for the transit into mitosis. At mitotic commitment, Cdk1p participates in its own regulation by activating the mitotic inducing phosphatase, Cdc25p, and inhibiting the opposing kinase, Wee1p. We have investigated the ability of Schizosaccharomyces pombe Clp1p, a Cdc14p homolog, to disrupt this auto-amplification loop. We show here that Clp1p is required to dephosphorylate, destabilize, and inactivate Cdc25p at the end of mitosis. Clp1p promotes recognition of Cdc25p by the anaphase-promoting complex/cyclosome, an E3 ubiquitin ligase. Failure to inactivate and destabilize Cdc25p in late mitosis delays progression through anaphase, interferes with septation initiation network signaling, and additionally advances the commitment to mitotic entry in the next cycle. This may be a widely conserved mechanism whereby Cdc14 proteins contribute to Cdk1p inactivation.
Wolfe
Benjamin A
BA
Department of Cell and Developmental Biology, Vanderbilt University, Nashville, TN 37232, USA.
Gould
Kathleen L
KL
D016203:CDC2 Protein Kinase / Q000378:metabolism; D018797:Cell Cycle Proteins / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism*; D005656:Fungal Proteins / Q000037:antagonists & inhibitors* / Q000235:genetics; D016195:G2 Phase; D008938:Mitosis; D009154:Mutation; D010766:Phosphorylation; D011485:Protein Binding; D017027:Protein Tyrosine Phosphatases / Q000235:genetics / Q000378:metabolism*; D012568:Schizosaccharomyces / Q000235:genetics / Q000378:metabolism*; D029702:Schizosaccharomyces pombe Proteins / Q000235:genetics / Q000378:metabolism*; D044767:Ubiquitin-Protein Ligases / Q000378:metabolism; D014452:Ubiquitins / Q000378:metabolism; D020666:ras-GRF1 / Q000037:antagonists & inhibitors* / Q000235:genetics
D018797:Cell Cycle Proteins; D005656:Fungal Proteins; D029702:Schizosaccharomyces pombe Proteins; D014452:Ubiquitins; D020666:ras-GRF1; D044767:Ubiquitin-Protein Ligases; D016203:CDC2 Protein Kinase; C439269:Clp1 protein, S. pombe; D017027:Protein Tyrosine Phosphatases