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PNAS 101 (12): 4124-4129

Copyright © 2004 by the National Academy of Sciences.


Coupling morphogenesis to mitotic entry

Krisada Sakchaisri*,{dagger}, Satoshi Asano*, Li-Rong Yu{ddagger}, Mark J. Shulewitz§, Chong J. Park*, Jung-Eun Park*, Young-Wook Cho*, Timothy D. Veenstra{ddagger}, Jeremy Thorner§, and Kyung S. Lee*

*Laboratory of Metabolism, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892; {ddagger}Mass Spectrometry Center, National Cancer Institute–Frederick, Frederick, MD 21702; §Department of Molecular and Cell Biology, University of California, Berkeley, CA 94720; and {dagger}Department of Pharmacology, Faculty of Science, Mahidol University, Bangkok 10400, Thailand

Received for publication December 22, 2003.

Abstract: In eukaryotes, cyclin B-bound cyclin-dependent protein kinase 1 promotes mitotic entry but is held in check, in part, by Wee1 protein kinase. Timely mitotic entry in budding yeast requires inactivation of Swe1 (Wee1 ortholog). Perturbations of the septin collar at the bud neck lead to Swe1 stabilization, delaying the G2/M transition. Swe1 is recruited to the neck and hyperphosphorylated before ubiquitin-mediated degradation. Hsl1 kinase (Nim1 ortholog), a negative regulator of Wee1, is required for efficient Swe1 localization at the neck but seems not to phosphorylate Swe1. Here, we show that two other kinases targeted sequentially to the neck, Cla4/PAK and Cdc5/Polo, are responsible for stepwise phosphorylation and down-regulation of Swe1. This mechanism links assembly of a cellular structure to passage into mitosis.

Key Words: Cdk1 regulation • mitotic progression • G2/M transition • Saccharomyces cerevisiae

To whom correspondence should be addressed at: Laboratory of Metabolism, Center for Cancer Research, National Cancer Institute, National Institutes of Health, 9000 Rockville Pike, Building 37, Room 3118, Bethesda, MD 20892. E-mail: kyunglee{at} or kyunglee{at}

Communicated by Alexander N. Glazer, University of California System, Oakland, CA, January 28, 2004

Abbreviation: Clb, cyclin B.

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