Integration of Cell Cycle Signals

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Science  09 Apr 2004:
Vol. 304, Issue 5668, pp. 175
DOI: 10.1126/science.304.5668.175b

Cell division in budding yeast depends on the formation of a filamentous collar containing septin proteins. This collar forms at the base of the emerging bud, marking the place in the membrane that constricts during cytokinesis, giving rise to mother and daughter cells when mitosis is complete. Protein complexes formed with septins are critical in coordinating morphogenesis with cell division. Sakchaisri et al. show that yeast cells use the status of multiple phosphorylation sites on the protein kinase Swe1 to keep track of cell cycle progression and of the assembly of complexes at the bud neck. Genetic analysis and use of a designed form of protein kinase Cla4 sensitive to a specific inhibitor showed that the Cla4 protein contributes to phosphorylation of Swe1 during S phase of the cell cycle. Depletion of another protein kinase, Cdc5, prevented the further phosphorylation of Swe1 that normally occurs right before entry into mitosis. Thus, accumulation of highly phosphorylated Swe1 provides the cell with an indicator that the cycle is progressing properly and that the necessary components are assembled in septin complexes. These phosphorylation events tag Swe1 for ubiquitin-dependent degradation, which in turn relieves Swe1's inhibitory phosphorylation of the critical cyclin-dependent kinase (Cdc28) that controls the initiation of mitosis. Watanabe et al. show that similar regulation occurs in human cells where degradation of the human Swe1 homolog Wee1A by the Cdc5 homolog polo-like kinase 1 is also critical for regulation of mitotic entry. — LBR

Proc. Natl. Acad. Sci. U.S.A. 101, 4124; 4419 (2004).

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