title: Inhibition of Cdc42 during mitotic exit is required for cytokinesis.
abstract: The role of Cdc42 and its regulation during cytokinesis is not well understood. Using biochemical and imaging approaches in budding yeast, we demonstrate that Cdc42 activation peaks during the G1/S transition and during anaphase but drops during mitotic exit and cytokinesis. Cdc5/Polo kinase is an important upstream cell cycle regulator that suppresses Cdc42 activity. Failure to down-regulate Cdc42 during mitotic exit impairs the normal localization of key cytokinesis regulators-Iqg1 and Inn1-at the division site, and results in an abnormal septum. The effects of Cdc42 hyperactivation are largely mediated by the Cdc42 effector p21-activated kinase Ste20. Inhibition of Cdc42 and related Rho guanosine triphosphatases may be a general feature of cytokinesis in eukaryotes.
authors.affiliation: Department of Pediatric Oncology, Dana-Farber Cancer Institute and Harvard Medical School, Boston, MA 02115, USA.
authors.forename: Benjamin D
authors.initials: BD
authors.lastname: Atkins
authors.forename: Satoshi
authors.initials: S
authors.lastname: Yoshida
authors.forename: Koji
authors.initials: K
authors.lastname: Saito
authors.forename: Chi-Fang
authors.initials: CF
authors.lastname: Wu
authors.forename: Daniel J
authors.initials: DJ
authors.lastname: Lew
authors.forename: David
authors.initials: D
authors.lastname: Pellman
mesh_terms: D018797:Cell Cycle Proteins / Q000235:genetics / Q000378:metabolism; D003470:Culture Media / Q000378:metabolism; D048749:Cytokinesis; D004789:Enzyme Activation; D020690:GTPase-Activating Proteins / Q000235:genetics / Q000378:metabolism; D015971:Gene Expression Regulation, Enzymologic; D015966:Gene Expression Regulation, Fungal; D049452:Green Fluorescent Proteins / Q000235:genetics / Q000378:metabolism; D020930:MAP Kinase Kinase Kinases / Q000235:genetics / Q000378:metabolism; D008938:Mitosis; D021381:Protein Transport; D029701:Saccharomyces cerevisiae Proteins / Q000235:genetics / Q000378:metabolism; D004718:Saccharomycetales / Q000166:cytology / Q000201:enzymology* / Q000378:metabolism; D020846:cdc42 GTP-Binding Protein, Saccharomyces cerevisiae / Q000235:genetics / Q000378:metabolism*; D020703:ras GTPase-Activating Proteins / Q000235:genetics / Q000378:metabolism
chemical_list: C084219:BEM2 protein, S cerevisiae; D018797:Cell Cycle Proteins; D003470:Culture Media; D020690:GTPase-Activating Proteins; C101203:IQ motif containing GTPase activating protein 1; C528682:Inn1 protein, S cerevisiae; D029701:Saccharomyces cerevisiae Proteins; D020703:ras GTPase-Activating Proteins; D049452:Green Fluorescent Proteins; D020930:MAP Kinase Kinase Kinases; C078754:STE20 protein, S cerevisiae; D020846:cdc42 GTP-Binding Protein, Saccharomyces cerevisiae