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Vol. 16, Issue 12, 5465-5479, December 2005

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The Mitotic Exit Network Mob1p-Dbf2p Kinase Complex Localizes to the Nucleus and Regulates Passenger Protein Localization

Jan Stoepel ^*  , Michelle A. Ottey ^* , Cornelia Kurischko ^*, Philip Hieter , and Francis C. Luca ^*

^* Department of Animal Biology, School of Veterinary Medicine, University of Pennsylvania, Philadelphia, PA 19104; Michael Smith Laboratories, University of British Columbia, Vancouver, British Columbia V6T 1Z4, Canada

Submitted April 22, 2005; Revised August 24, 2005; Accepted September 11, 2005
Monitoring Editor: Kerry Bloom

The Saccharomyces cerevisiae mitotic exit network (MEN) is a conserved signaling network that coordinates CDK inactivation, cytokinesis and G1 gene transcription. The MEN Cdc14p phosphatase is sequestered in the nucleolus and transiently released in early anaphase and telophase. Cdc14p mediates mitotic exit by dephosphorylating Cdk1p substrates and promoting Cdk1p inactivation. Cdc14p also regulates the localization of chromosomal passenger proteins, which redistribute from kinetochores to the mitotic spindle during anaphase. Here we present evidence that the MEN protein kinase complex Mob1p-Dbf2p localizes to mitotic nuclei and partially colocalizes with Cdc14p and kinetochore proteins. Chromatin immunoprecipitation (ChIP) experiments reveal that Mob1p, Dbf2p, and Cdc14p associate with centromere DNA and require the centromere binding protein Ndc10p for this association. We establish that Mob1p is essential for maintaining the localization of Aurora, INCENP, and Survivin chromosomal passenger proteins on anaphase spindles, whereas Cdc14p and the Mob1p-Dbf2p-activating kinase Cdc15p are required for establishing passenger protein localization on the spindle. Moreover, Mob1p, but not Cdc15p, is required for dissociating Aurora from the kinetochore region. These findings reveal kinetochores as sites for MEN signaling and implicate MEN in coordinating chromosome segregation and/or spindle integrity with mitotic exit and cytokinesis via regulation of chromosome passenger proteins.

Abbreviations used: MEN, mitotic exit network; SPB, spindle pole body; ChIP, chromatin immunoprecipitation.

The online version of this article contains supplemental material at MBC Online (http://www.molbiolcell.org).

These authors contributed equally to this work.

Address correspondence to: Francis C. Luca (fluca{at}vet.upenn.edu).

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