title: Loss of CDC5 function in Saccharomyces cerevisiae leads to defects in Swe1p regulation and Bfa1p/Bub2p-independent cytokinesis.
abstract: In many organisms, polo kinases appear to play multiple roles during M-phase progression. To provide new insights into the function of budding yeast polo kinase Cdc5p, we generated novel temperature-sensitive cdc5 mutants by mutagenizing the C-terminal domain. Here we show that, at a semipermissive temperature, the cdc5-3 mutant exhibited a synergistic bud elongation and growth defect with loss of HSL1, a component important for normal G(2)/M transition. Loss of SWE1, which phosphorylates and inactivates the budding yeast Cdk1 homolog Cdc28p, suppressed the cdc5-3 hsl1Delta defect, suggesting that Cdc5p functions at a point upstream of Swe1p. In addition, the cdc5-4 and cdc5-7 mutants exhibited chained cell morphologies with shared cytoplasms between the connected cell bodies, indicating a cytokinetic defect. Close examination of these mutants revealed delayed septin assembly at the incipient bud site and loosely organized septin rings at the mother-bud neck. Components in the mitotic exit network (MEN) play important roles in normal cytokinesis. However, loss of BFA1 or BUB2, negative regulators of the MEN, failed to remedy the cytokinetic defect of these mutants, indicating that Cdc5p promotes cytokinesis independently of Bfa1p and Bub2p. Thus, Cdc5p contributes to the activation of the Swe1p-dependent Cdc28p/Clb pathway, normal septin function, and cytokinesis.
authors.affiliation: Laboratory of Metabolism, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892, USA.
authors.forename: Chong Jin
authors.initials: CJ
authors.lastname: Park
authors.forename: Sukgil
authors.initials: S
authors.lastname: Song
authors.forename: Philip R
authors.initials: PR
authors.lastname: Lee
authors.forename: Wenying
authors.initials: W
authors.lastname: Shou
authors.forename: Raymond J
authors.initials: RJ
authors.lastname: Deshaies
authors.forename: Kyung S
authors.initials: KS
authors.lastname: Lee
mesh_terms: D017489:CDC28 Protein Kinase, S cerevisiae / Q000378:metabolism; D018797:Cell Cycle Proteins / Q000378:metabolism; D002455:Cell Division / Q000235:genetics*; D019926:Cyclin B / Q000378:metabolism; D003598:Cytoskeletal Proteins / Q000378:metabolism; D015966:Gene Expression Regulation, Fungal; D008938:Mitosis / Q000235:genetics / Q000502:physiology; D009154:Mutation; D011494:Protein Kinases / Q000235:genetics / Q000378:metabolism*; D017346:Protein Serine-Threonine Kinases; D011505:Protein-Tyrosine Kinases / Q000235:genetics / Q000378:metabolism*; D012441:Saccharomyces cerevisiae / Q000201:enzymology / Q000235:genetics / Q000378:metabolism*; D029701:Saccharomyces cerevisiae Proteins / Q000378:metabolism
chemical_list: C119117:BFA1 protein, S cerevisiae; C070351:BUB2 protein, S cerevisiae; C093749:CLB2 protein, S cerevisiae; D018797:Cell Cycle Proteins; D019926:Cyclin B; D003598:Cytoskeletal Proteins; D029701:Saccharomyces cerevisiae Proteins; D011494:Protein Kinases; C099685:SWE1 protein, S cerevisiae; D011505:Protein-Tyrosine Kinases; D017346:Protein Serine-Threonine Kinases; C081927:CDC5 protein, S cerevisiae; D017489:CDC28 Protein Kinase, S cerevisiae