Cdk and APC activities limit the spindle-stabilizing function of Fin1 to anaphase.
The fidelity of chromosome segregation depends on proper regulation of mitotic spindle behaviour. In anaphase, spindle stability is promoted by the dephosphorylation of cyclin-dependent kinase (Cdk) substrates, which results from Cdk inactivation and phosphatase activation. Few of the critical Cdk targets have been identified. Here, we identify the budding-yeast protein Fin1 (ref. 7) as a spindle-stabilizing protein whose activity is strictly limited to anaphase by changes in its phosphorylation state and rate of degradation. Phosphorylation of Fin1 from S phase to metaphase, by the cyclin-dependent kinase Clb5-Cdk1, inhibits Fin1 association with the spindle. In anaphase, when Clb5-Cdk1 is inactivated, Fin1 is dephosphorylated by the phosphatase Cdc14. Fin1 dephosphorylation targets it to the poles and microtubules of the elongating spindle, where it contributes to spindle integrity. A non-phosphorylatable Fin1 mutant localizes to the spindle before anaphase and impairs efficient chromosome segregation. As cells complete mitosis and disassemble the spindle, the ubiqutin ligase APC(Cdh1) targets Fin1 for destruction. Our studies illustrate how phosphorylation-dependent changes in the behaviour of Cdk1 substrates influence complex mitotic processes.
Woodbury
Erika L
EL
Department of Physiology, University of California, UCSF Mailcode 2200, Genentech Hall Room N312B, 600 16th Street, San Francisco, CA 94158-2517, USA.
Morgan
David O
DO
D000705:Anaphase / Q000235:genetics*; D016203:CDC2 Protein Kinase / Q000378:metabolism; D064199:Cdc20 Proteins; D064200:Cdh1 Proteins; D018797:Cell Cycle Proteins; D019926:Cyclin B / Q000378:metabolism; D018844:Cyclin-Dependent Kinases / Q000378:metabolism / Q000502:physiology*; D003598:Cytoskeletal Proteins / Q000235:genetics / Q000378:metabolism*; D008870:Microtubules / Q000378:metabolism; D008938:Mitosis / Q000235:genetics; D009154:Mutation; D010766:Phosphorylation; D012441:Saccharomyces cerevisiae / Q000235:genetics / Q000378:metabolism*; D029701:Saccharomyces cerevisiae Proteins / Q000235:genetics / Q000378:metabolism* / Q000502:physiology; D008941:Spindle Apparatus / Q000235:genetics / Q000378:metabolism*; D044767:Ubiquitin-Protein Ligases / Q000378:metabolism
C577495:CDC20 protein, S cerevisiae; C577583:CDH1 protein, S cerevisiae; C076558:CLB5 protein, S cerevisiae; D064199:Cdc20 Proteins; D064200:Cdh1 Proteins; D018797:Cell Cycle Proteins; D019926:Cyclin B; D003598:Cytoskeletal Proteins; C456282:FIN1 protein, S cerevisiae; D029701:Saccharomyces cerevisiae Proteins; D044767:Ubiquitin-Protein Ligases; D016203:CDC2 Protein Kinase; D018844:Cyclin-Dependent Kinases