Phospho-regulation of the Cdc14/Clp1 phosphatase delays late mitotic events in S. pombe.
In eukaryotes, exit from mitosis occurs through the inactivation of the Cdk1-cyclin B kinase complex and the reversal of its phosphorylation events. These late mitotic events are tightly regulated to occur only after the onset of anaphase and prior to cytokinesis. Central to this regulation is the conserved Cdc14 family of protein phosphatases, whose activity reverses Cdk-dependent phosphorylation events. S. cerevisiae Cdc14 activity is restrained from dephosphorylating Cdk substrates and inactivating Cdk1 through its nucleolar sequestration prior to anaphase. Here, we describe a unique mode of Cdc14 regulation that operates prior to anaphase in fission yeast. Cdk1 phosphorylates and inhibits the catalytic activity of the Cdc14 family member, Clp1/Flp1. As Cdk1 activity declines during anaphase progression, Clp1/Flp1 autocatalytically reverses these phosphorylation events to stimulate its own activity. These findings point to a simple regulatory circuit that couples Cdk1 activation with its inactivation mediated through phosphorylation-dependent regulation of Clp1/Flp1 phosphatase activity.
Wolfe
Benjamin A
BA
Department of Cell and Developmental Biology, Vanderbilt University School of Medicine, Medical Center North B-2309, 1161 21st Avenue South, Nashville, Tennessee 37232, USA.
McDonald
W Hayes
WH
Yates
John R
JR
Gould
Kathleen L
KL
D016203:CDC2 Protein Kinase / Q000378:metabolism; D002453:Cell Cycle; D018797:Cell Cycle Proteins / Q000378:metabolism*; D020090:Chromosome Segregation; D004789:Enzyme Activation; D015966:Gene Expression Regulation, Fungal; D008938:Mitosis; D008954:Models, Biological; D010749:Phosphoprotein Phosphatases / Q000378:metabolism*; D010766:Phosphorylation; D017027:Protein Tyrosine Phosphatases / Q000378:metabolism*; D012568:Schizosaccharomyces / Q000201:enzymology* / Q000235:genetics / Q000378:metabolism; D029702:Schizosaccharomyces pombe Proteins / Q000378:metabolism*
D018797:Cell Cycle Proteins; D029702:Schizosaccharomyces pombe Proteins; D016203:CDC2 Protein Kinase; C503885:CDC14 protein, S pombe; D010749:Phosphoprotein Phosphatases; C439269:Clp1 protein, S. pombe; D017027:Protein Tyrosine Phosphatases