Fission yeast nucleolar protein Dnt1 regulates G2/M transition and cytokinesis by downregulating Wee1 kinase
Fission yeast nucleolar protein Dnt1 regulates G2/M transition and cytokinesis by downregulating Wee1 kinase
复制标题
DOI：
10.1242/jcs.132845
复制
发表时间：
2013-11
影响因子：
4
通讯作者：
ZHI-YONG Yu;Mengling Zhang;Gao-yuan Wang;Dan Xu;Daniel Keifenheim;A. Franco;J. Cansado;H. Masuda;N. Rhind;Yamei Wang;Q. Jin
中科院分区：
文献类型：
--
作者：
ZHI-YONG Yu;Mengling Zhang;Gao-yuan Wang;Dan Xu;Daniel Keifenheim;A. Franco;J. Cansado;H. Masuda;N. Rhind;Yamei Wang;Q. Jin
胞质分裂涉及细胞周期、细胞骨架和膜系统在时间和空间上的协调作用，以实现子细胞的分离。在粟酒裂殖酵母和酿酒酵母中，分隔起始网络（SIN）和有丝分裂退出网络（MEN）信号通路分别调节胞质分裂和有丝分裂退出。以前，我们已经表明，在裂变酵母，核仁蛋白Dnt 1负调控SIN途径的方式是独立的Cdc 14家族磷酸酶Clp 1/Flp 1，但Dnt 1如何调节这一途径仍然难以捉摸。相比之下，很明显，它的芽殖酵母亲戚，Net 1/Cfi 1，调节同源MEN信号通路，在有丝分裂退出前，在核仁中螯合Cdc 14磷酸酶。在这项研究中，我们发现，dnt 1+正调控细胞周期中的G2/M转换。通过进行上位性分析来测量双突变体（dnt 1和G2/M控制中涉及的基因）细胞中分隔时的细胞长度，我们发现dnt 1+和wee 1+之间存在联系。此外，我们发现，有丝分裂抑制剂Wee 1激酶的蛋白水平升高和Cdk 1活性的相应衰减是负责拯救效应的dnt 1 SIN突变体。最后，我们的数据还表明，Dnt 1调节Wee 1活性与SCF介导的Wee 1降解平行。因此，这项研究揭示了核仁蛋白Dnt 1和SIN信号通路之间意外缺失的环节，这是由Cdk 1调节剂Wee 1激酶介导的。我们的研究结果还定义了一种新的模式的调节Wee 1和Cdk 1，这是重要的整合信号控制的SIN途径在裂殖酵母。
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 dnt1&Dgr; 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.