Fission yeast Clp1p phosphatase regulates G2/M transition and coordinationof cytokinesis with cell cycle progression

Background: In Saccharomyces cerevisiae the mitotic-exit network (MEN) func tions in anaphase to promote the release of the Cdc14p phosphatase from the nucleolus, This release causes mitotic exit via inactivation of the cyclin -dependent kinase (Cdk). Cdc14p-like proteins are highly conserved; however , it is unclear if these proteins regulate mitotic exit as in S. cerevisiae , In Schizosaccharomyces pombe a signaling pathway homologous to the MEN an d termed the septation initiation network (SIN) is required not for mitotic exit, but for initiation of cytokinesis and for a cytokinesis checkpoint t hat inhibits further cell cycle progression until cytokinesis is complete. Results: We have identified the S. pombe Cdc14p homolog, Clp1p, and show th at it is not required for mitotic exit but rather functions together with t he SIN in coordinating cytokinesis with the nuclear-division cycle. As cell s enter mitosis, Clp1p relocalizes from the nucleolus to the spindle and si te of cell division, Clp1p exit from the nucleolus does not depend on the S IN, but the SIN is required for keeping Clp1p out of the nucleolus until co mpletion of cytokinesis. Clp1p, in turn, may promote the activation of the SIN by antagonizing Cdk activity until cytokinesis is complete and thus ens uring that cytokinesis is completed prior to the initiation of the next cel l cycle. In addition to its roles in anaphase, Clp1p regulates the G2/M tra nsition since cells deleted for clp1 enter mitosis precociously and cells o verexpressing Clp1p delay mitotic entry. Unlike Cdc14p, Clp1p appears to an tagonize Cdk activity by preventing dephosphorylation of Cdc2p on tyrosine. Conclusions: S. pombe Clp1p affects cell cycle progression in a markedly di fferent manner than its S. cerevisiae homolog, Cdc14p. This finding raises the possibility that related phosphatases in animal cells will prove to hav e important roles in coordinating the onset of cytokinesis with the events of mitosis. (C) 2001 Elsevier Science Ltd. All rights reserved.