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Science 305 (5683): 516-519

Copyright © 2004 by the American Association for the Advancement of Science

Phosphorylation by Cyclin B-Cdk Underlies Release of Mitotic Exit Activator Cdc14 from the Nucleolus

Ramzi Azzam,1 Susan L. Chen,3 Wenying Shou,1 Angie S. Mah,1 Gabriela Alexandru,1,4 Kim Nasmyth,4 Roland S. Annan,3 Steven A. Carr,3* Raymond J. Deshaies1,2{dagger}

Abstract: Budding yeast protein phosphatase Cdc14 is sequestered in the nucleolus in an inactive state during interphase by the anchor protein Net1. Upon entry into anaphase, the Cdc14 early anaphase release (FEAR) network initiates dispersal of active Cdc14 throughout the cell. We report that the FEARnetwork promotes phosphorylation of Net1 by cyclin-dependent kinase (Cdk) complexed with cyclin B1 or cyclin B2. These phosphorylations appear to be required for FEAR and sustain the proper timing of late mitotic events. Thus, a regulatory circuit exists to ensure that the arbiter of the mitotic state, Cdk, sets in motion events that culminate in exit from mitosis.

1 Division of Biology, California Institute of Technology, Pasadena, CA 91125, USA.
2 Howard Hughes Medical Institute, California Institute of Technology, Pasadena, CA 91125, USA.
3 Department of Computational, Analytical, and Structural Sciences, GlaxoSmithKline, King of Prussia, PA 19406, USA.
4 Research Institute of Molecular Pathology, Dr. Bohr-Gasse 7, A-1030, Vienna, Austria.

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* Present address: Broad Institute, 320 Charles Street, Cambridge, MA 02139, USA.

{dagger} To whom correspondence should be addressed. E-mail: deshaies{at}caltech.edu

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