Fission yeast nucleolar protein Dnt1 regulates G2/M transition and cytokinesis by downregulating wee1 kinase

Zhi yong Yu, Meng ting Zhang, Gao yuan Wang, Dan Xu, Daniel Keifenheim, Alejandro Franco, Jose Cansado, Hirohisa Masuda, Nick Rhind, Yamei Wang, Quan wen Jin

Research output: Contribution to journalArticle

5 Citations (Scopus)

Abstract

Summary: 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.

Original languageEnglish (US)
Pages (from-to)4995-5004
Number of pages10
JournalJournal of cell science
Volume126
Issue number21
DOIs
StatePublished - Nov 1 2013

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Schizosaccharomyces pombe Proteins
Cytokinesis
Schizosaccharomyces
Nuclear Proteins
Phosphoric Monoester Hydrolases
Cell Cycle
Phosphotransferases
Down-Regulation
Saccharomycetales
Cell Separation
Saccharomyces cerevisiae
Yeasts
Cell Membrane
Genes
Proteins

Keywords

  • Cytokinesis
  • Dnt1
  • Fission yeast
  • G2/M transition
  • Nucleolus
  • Wee1

Cite this

Fission yeast nucleolar protein Dnt1 regulates G2/M transition and cytokinesis by downregulating wee1 kinase. / Yu, Zhi yong; Zhang, Meng ting; Wang, Gao yuan; Xu, Dan; Keifenheim, Daniel; Franco, Alejandro; Cansado, Jose; Masuda, Hirohisa; Rhind, Nick; Wang, Yamei; Jin, Quan wen.

In: Journal of cell science, Vol. 126, No. 21, 01.11.2013, p. 4995-5004.

Research output: Contribution to journalArticle

Yu, ZY, Zhang, MT, Wang, GY, Xu, D, Keifenheim, D, Franco, A, Cansado, J, Masuda, H, Rhind, N, Wang, Y & Jin, QW 2013, 'Fission yeast nucleolar protein Dnt1 regulates G2/M transition and cytokinesis by downregulating wee1 kinase', Journal of cell science, vol. 126, no. 21, pp. 4995-5004. https://doi.org/10.1242/jcs.132845
Yu, Zhi yong ; Zhang, Meng ting ; Wang, Gao yuan ; Xu, Dan ; Keifenheim, Daniel ; Franco, Alejandro ; Cansado, Jose ; Masuda, Hirohisa ; Rhind, Nick ; Wang, Yamei ; Jin, Quan wen. / Fission yeast nucleolar protein Dnt1 regulates G2/M transition and cytokinesis by downregulating wee1 kinase. In: Journal of cell science. 2013 ; Vol. 126, No. 21. pp. 4995-5004.
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T1 - Fission yeast nucleolar protein Dnt1 regulates G2/M transition and cytokinesis by downregulating wee1 kinase

AU - Yu, Zhi yong

AU - Zhang, Meng ting

AU - Wang, Gao yuan

AU - Xu, Dan

AU - Keifenheim, Daniel

AU - Franco, Alejandro

AU - Cansado, Jose

AU - Masuda, Hirohisa

AU - Rhind, Nick

AU - Wang, Yamei

AU - Jin, Quan wen

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N2 - Summary: 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.

AB - Summary: 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.

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