Journal
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
Volume 101, Issue 12, Pages 4124-4129Publisher
NATL ACAD SCIENCES
DOI: 10.1073/pnas.0400641101
Keywords
Cdk1 regulation; mitotic progression; G(2)/M transtion; Saccharomyces cerevisiae
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Funding
- NIGMS NIH HHS [GM 21841, R01 GM021841] Funding Source: Medline
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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 Swell (Wee1 ortholog). Perturbations of the septin collar at the bud neck lead to Swe1 stabilization, delaying the G(2)/M transition. Swell is recruited to the neck and hyperphosphorylated before ubiquitin-mediated degradation. Hsl1 kinase (Nim1 ortholog), a negative regulator of Wee1, is required for efficient Swell 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 Swell. This mechanism links assembly of a cellular structure to passage into mitosis.
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