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Vol. 19, Issue 9, 4006-4018, September 2008

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Nucleocytoplasmic Trafficking of G2/M Regulators in Yeast

Mignon A. Keaton^*, Lee Szkotnicki, Aron R. Marquitz, Jake Harrison, Trevin R. Zyla, and Daniel J. Lew

Department of Pharmacology and Cancer Biology, Duke University Medical Center, Durham, NC 27710

Submitted March 17, 2008; Revised June 5, 2008; Accepted June 9, 2008
Monitoring Editor: Mark J. Solomon

Nucleocytoplasmic shuttling is prevalent among many cell cycle regulators controlling the G2/M transition. Shuttling of cyclin/cyclin-dependent kinase (CDK) complexes is thought to provide access to substrates stably located in either compartment. Because cyclin/CDK shuttles between cellular compartments, an upstream regulator that is fixed in one compartment could in principle affect the entire cyclin/CDK pool. Alternatively, the regulators themselves may need to shuttle to effectively regulate their moving target. Here, we identify localization motifs in the budding yeast Swe1p (Wee1) and Mih1p (Cdc25) cell cycle regulators. Replacement of endogenous Swe1p or Mih1p with mutants impaired in nuclear import or export revealed that the nuclear pools of Swe1p and Mih1p were more effective in CDK regulation than were the cytoplasmic pools. Nevertheless, shuttling of cyclin/CDK complexes was sufficiently rapid to coordinate nuclear and cytoplasmic events even when Swe1p or Mih1p were restricted to one compartment. Additionally, we found that Swe1p nuclear export was important for its degradation. Because Swe1p degradation is regulated by cytoskeletal stress, shuttling of Swe1p between nucleus and cytoplasm serves to couple cytoplasmic stress to nuclear cyclin/CDK inhibition.

Present addresses: * Department of Biochemistry and Molecular Genetics, University of Virginia, Charlottesville, VA 22908;

Lineberger Comprehensive Cancer Center, University of North Carolina, Chapel Hill, NC 27599;

Microbia Precision Engineering, Inc., Lexington, MA 02421; and

Duke-NUS Graduate Medical School Singapore, Singapore 169612.

Address correspondence to: Daniel J. Lew (daniel.lew{at}duke.edu)

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