Novel regulation of mitotic exit by the Cdc42 effectors Gic1 and Gic2.
The guanine nucleotide exchange factor Cdc24, the GTPase Cdc42, and the Cdc42 effectors Cla4 and Ste20, two p21-activated kinases, form a signal transduction cascade that promotes mitotic exit in yeast. We performed a genetic screen to identify components of this pathway. Two related bud cortex-associated Cdc42 effectors, Gic1 and Gic2, were obtained as factors that promoted mitotic exit independently of Ste20. The mitotic exit function of Gic1 was dependent on its activation by Cdc42 and on the release of Gic1 from the bud cortex. Gic proteins became essential for mitotic exit when activation of the mitotic exit network through Cdc5 polo kinase and the bud cortex protein Lte1 was impaired. The mitotic exit defect of cdc5-10 Deltalte1 Deltagic1 Deltagic2 cells was rescued by inactivation of the inhibiting Bfa1-Bub2 GTPase-activating protein. Moreover, Gic1 bound directly to Bub2 and prevented binding of the GTPase Tem1 to Bub2. We propose that in anaphase the Cdc42-regulated Gic proteins trigger mitotic exit by interfering with Bfa1-Bub2 GTPase-activating protein function.
Höfken
Thomas
T
The Paterson Institute for Cancer Research, Christie Hospital NHS Trust, Wilmslow Rd., Manchester, M20 4BX, UK.
Schiebel
Elmar
E
D048868:Adaptor Proteins, Signal Transducing; D002352:Carrier Proteins / Q000378:metabolism*; D002453:Cell Cycle / Q000502:physiology*; D005838:Genotype; D006706:Homeostasis; D008938:Mitosis / Q000502:physiology*; D008954:Models, Biological; D010641:Phenotype; D012441:Saccharomyces cerevisiae / Q000166:cytology* / Q000235:genetics / Q000502:physiology; D029701:Saccharomyces cerevisiae Proteins / Q000378:metabolism*; D020764:cdc42 GTP-Binding Protein / Q000378:metabolism*
D048868:Adaptor Proteins, Signal Transducing; D002352:Carrier Proteins; C109252:GIC1 protein, S cerevisiae; C109253:GIC2 protein, S cerevisiae; D029701:Saccharomyces cerevisiae Proteins; D020764:cdc42 GTP-Binding Protein