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Published online September 1, 2008
doi:10.1083/jcb.200801054
The Journal of Cell Biology, Vol. 182, No. 5, 873-883
The Rockefeller University Press, 0021-9525 $30.00
© 2008 Queralt et al.
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Article

Separase cooperates with Zds1 and Zds2 to activate Cdc14 phosphatase in early anaphase



Ethel Queralt1,2 and Frank Uhlmann1

1 Chromosome Segregation Laboratory, Cancer Research UK London Research Institute, London WC2A 3PX, England, UK
2 Cancer Epigenetics and Biology Program, Catalan Institute of Oncology, 08907 L'Hospitalet de Llobregat, Spain

Correspondence to Ethel Queralt: equeralt{at}iconcologia.net; or Frank Uhlmann: frank.uhlmann{at}cancer.org.uk

Completion of mitotic exit and cytokinesis requires the inactivation of mitotic cyclin-dependent kinase (Cdk) activity. A key enzyme that counteracts Cdk during budding yeast mitotic exit is the Cdc14 phosphatase. Cdc14 is inactive for much of the cell cycle, sequestered by its inhibitor Net1 in the nucleolus. At anaphase onset, separase-dependent down-regulation of PP2ACdc55 allows phosphorylation of Net1 and consequent Cdc14 release. How separase causes PP2ACdc55 down-regulation is not known. Here, we show that two Cdc55-interacting proteins, Zds1 and Zds2, contribute to timely Cdc14 activation during mitotic exit. Zds1 and Zds2 are required downstream of separase to facilitate nucleolar Cdc14 release. Ectopic Zds1 expression in turn is sufficient to down-regulate PP2ACdc55 and promote Net1 phosphorylation. These findings identify Zds1 and Zds2 as new components of the mitotic exit machinery, involved in activation of the Cdc14 phosphatase at anaphase onset. Our results suggest that these proteins may act as separase-regulated PP2ACdc55 inhibitors.

Abbreviations used in this paper: APC, anaphase-promoting complex; MEN, mitotic exit network; PAK, p21-activated kinase; PP2A, type 2A protein phosphatase.

© 2008 Queralt and Uhlmann This article is distributed under the terms of an Attribution–Noncommercial–Share Alike–No Mirror Sites license for the first six months after the publication date (see http://www.jcb.org/misc/terms.shtml). After six months it is available under a Creative Commons License (Attribution–Noncommercial–Share Alike 3.0 Unported license, as described at http://creativecommons.org/licenses/by-nc-sa/3.0/).


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