Proceedings of the National Academy of Sciences · 2004 · 125 citations · 38 references
Life SciencesCell BiologyMolecular BiologyCell DivisionCell SignalingMorphogenesisCell Cycle ControlCell Cycle TransitionsCell-cycle RegulationMitosisMitotic EntryProtein Kinase CascadesCyclin-dependent Kinase 1 ActivationM TransitionMitosis RegulationMitotic Entry ControlMitotic Entry RegulationSeptin BiologyStabilizationWee1 Kinase Regulation
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 G(2)/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.
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Multisite phosphorylation of a CDK inhibitor sets a threshold for the onset of DNA replication
Piers Nash, Xiaojing Tang, Stephen Orlicky et al. · Nature · 2001 · 759 citations