Fission yeast nucleolar protein Dnt1 regulates G2/M transition and cytokinesis by downregulating Wee1 kinase
Journal of Cell Science (Impact Factor: 5.43). 09/2013; 126(21). DOI: 10.1242/jcs.132845
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 SIN pathway in a manner independent of Cdc14-family phosphatase Clp1/Flp1, but the detailed mechanism of how Dnt1 modulates this pathway has remained elusive. In contrast, it is clear that its budding yeast relative, Net1/Cfi1, regulates the homologous MEN signaling pathway through sequestering the Cdc14 phosphatase in the nucleolus before mitotic exit. In this study, we have obtained evidence indicating that dnt1(+) positively regulates the G2/M transition during cell cycle. By conducting epistasis analyses measuring the cell length at division of double mutants between dnt1Δ and genes involved in G2/M control, we found a link between dnt1(+) and wee1(+). Furthermore, we showed that elevated protein level of 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 Cdk1 regulator Wee1 kinase. Our findings also define a novel mode of Wee1/Cdk1 regulation which is important for the integration of signals controlling SIN pathway in fission yeast.
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ABSTRACT: Modification of cell cycle in entomopathogenic fungi is likely crucial for host infection and environmental adaptation. Here we show that Wee1 and Cdc25 can balance cell cycle-required Cdk1 activity in Beauveria bassiana. The Cdk1 phosporylation signal was strong in Δcdc25 but very weak in Δwee1 and absent in Δwee1Δcdc25. Consequently, cell cycles, septation patterns, and many septation-dependent gene transcripts of these mutants were reversely changed. Hyphal cells were short in Δwee1, slender in Δcdc25, and short and swollen in Δwee1Δcdc25. Conidiation was most defective in Δwee1, followed by Δcdc25. Their conidia and yeast-like blastospores also altered antagonistically in both size and complexity, accompanied with abnormally branched germlings in Δwee1 and Δwee1Δcdc25. Conidial thermotolerance and UV-B resistance decreased much more in Δwee1Δcdc25 than in Δwee1 but significantly increased in Δcdc25. The double deletion and the point mutation Cdk1(T14A/P15F) for inhibitory phosphorylation caused most defective virulence, followed by wee1 deletion. All the changes were restored by ectopic gene complementation. Virulence changes in all the mutants and control strains were highly correlated to those in blastospore size or complexity. Taken together, Wee1 and Cdc25 control cell cycle, morphogenesis, asexual development, stress tolerance and virulence of B. bassiana by balancing the Cdk1 activity.Environmental Microbiology 06/2014; 17(4). DOI:10.1111/1462-2920.12530 · 6.20 Impact Factor
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