title: Fission yeast nucleolar protein Dnt1 regulates G2/M transition and cytokinesis by downregulating Wee1 kinase.
abstract: Cytokinesis involves temporally and spatially coordinated action of the cell cycle, cytoskeletal and membrane systems to achieve separation of daughter cells. The septation initiation network (SIN) and mitotic exit network (MEN) signaling pathways regulate cytokinesis and mitotic exit in the yeasts Schizosaccharomyces pombe and Saccharomyces cerevisiae, respectively. Previously, we have shown that in fission yeast, the nucleolar protein Dnt1 negatively regulates the SIN pathway in a manner that is independent of the Cdc14-family phosphatase Clp1/Flp1, but how Dnt1 modulates this pathway has remained elusive. By contrast, it is clear that its budding yeast relative, Net1/Cfi1, regulates the homologous MEN signaling pathway by sequestering Cdc14 phosphatase in the nucleolus before mitotic exit. In this study, we show that dnt1(+) positively regulates G2/M transition during the cell cycle. By conducting epistasis analyses to measure cell length at septation in double mutant (for dnt1 and genes involved in G2/M control) cells, we found a link between dnt1(+) and wee1(+). Furthermore, we showed that elevated protein levels of the mitotic inhibitor Wee1 kinase and the corresponding attenuation in Cdk1 activity is responsible for the rescuing effect of dnt1Δ on SIN mutants. Finally, our data also suggest that Dnt1 modulates Wee1 activity in parallel with SCF-mediated Wee1 degradation. Therefore, this study reveals an unexpected missing link between the nucleolar protein Dnt1 and the SIN signaling pathway, which is mediated by the Cdk1 regulator Wee1 kinase. Our findings also define a novel mode of regulation of Wee1 and Cdk1, which is important for integration of the signals controlling the SIN pathway in fission yeast.
authors.affiliation: State Key Laboratory of Cellular Stress Biology, School of Life Sciences, Xiamen University, Xiamen 361102, Fujian, China.
authors.forename: Zhi-Yong
authors.initials: ZY
authors.lastname: Yu
authors.forename: Meng-Ting
authors.initials: MT
authors.lastname: Zhang
authors.forename: Gao-Yuan
authors.initials: GY
authors.lastname: Wang
authors.forename: Dan
authors.initials: D
authors.lastname: Xu
authors.forename: Daniel
authors.initials: D
authors.lastname: Keifenheim
authors.forename: Alejandro
authors.initials: A
authors.lastname: Franco
authors.forename: Jose
authors.initials: J
authors.lastname: Cansado
authors.forename: Hirohisa
authors.initials: H
authors.lastname: Masuda
authors.forename: Nick
authors.initials: N
authors.lastname: Rhind
authors.forename: Yamei
authors.initials: Y
authors.lastname: Wang
authors.forename: Quan-Wen
authors.initials: QW
authors.lastname: Jin
mesh_terms: D018797:Cell Cycle Proteins / Q000235:genetics* / Q000378:metabolism; D002466:Cell Nucleolus / Q000235:genetics / Q000378:metabolism*; D015536:Down-Regulation; D016195:G2 Phase; D015966:Gene Expression Regulation, Fungal; D008540:Meiosis; D009687:Nuclear Proteins / Q000235:genetics* / Q000378:metabolism*; D011505:Protein-Tyrosine Kinases / Q000235:genetics* / Q000378:metabolism; D012568:Schizosaccharomyces / Q000166:cytology / Q000201:enzymology* / Q000235:genetics / Q000378:metabolism; D029702:Schizosaccharomyces pombe Proteins / Q000235:genetics* / Q000378:metabolism*
chemical_list: D018797:Cell Cycle Proteins; C523506:Dnt1 protein, S pombe; D009687:Nuclear Proteins; D029702:Schizosaccharomyces pombe Proteins; C068689:wee1 protein, S pombe; D011505:Protein-Tyrosine Kinases
keywords: Cytokinesis; Dnt1; Fission yeast; G2/M transition; Nucleolus; Wee1