Nim1-related kinases coordinate cell cycle progression with the organization of the peripheral cytoskeleton in yeast
Nim1-related kinases coordinate cell cycle progression with the organization of the peripheral cytoskeleton in yeast
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DOI：
10.1101/gad.13.2.176
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发表时间：
1999-01-15
影响因子：
10.5
通讯作者：
Snyder, M
中科院分区：
文献类型：
--
作者：
Barral, Y;Parra, M;Snyder, M
细胞周期进程与外周细胞骨架组织化的耦合机制知之甚少。在酿酒酵母中，Swe 1蛋白先前已被证明磷酸化和磷酸化细胞周期蛋白依赖性激酶Cdc 28，从而延迟有丝分裂的开始。nim 1相关的蛋白激酶Hsl 1通过负调节Swe 1诱导进入有丝分裂。我们已经发现，Hsl 1物理协会与septin细胞骨架在体内和Hsl 1激酶活性取决于适当的septin功能。遗传分析表明，两个额外的Hsl 1相关的激酶，Kcc 4和Gin 4，与Hsl 1冗余地调节Swe 1。Kcc 4，像Hsl 1和Gin 4，被发现本地化的芽颈在septin依赖的方式。有趣的是，hsl 1 kcc 4 gin 4三重突变体产生的细胞形态与septin突变体极其相似。与Hsl 1，Kcc 4和Gin 4链接进入有丝分裂到适当的septin组织的想法一致，我们发现，septin突变体在限制性温度下孵育触发了Swe 1依赖的有丝分裂延迟，这是维持细胞活力所必需的。这些结果首次揭示了细胞如何监测其细胞骨架的组织，并证明了细胞周期检查点的存在，该检查点对外周细胞骨架中的缺陷做出反应。此外，Hsl 1，Kcc 4和Gin 4在高等真核生物中具有同源物，表明这类激酶对Swe 1/Wee 1的调节是高度保守的。
The mechanisms that couple cell cycle progression with the organization of the peripheral cytoskeleton are poorly understood. In Saccharomyces cerevisiae, the Swe1 protein has been shown previously to phosphorylate and inactivate the cyclin-dependent kinase, Cdc28, thereby delaying the onset of mitosis. The nim1-related protein kinase, Hsl1, induces entry into mitosis by negatively regulating Swe1. We have found that Hsl1 physically associates with the septin cytoskeleton in vivo and that Hsl1 kinase activity depends on proper septin function. Genetic analysis indicates that two additional Hsl1-related kinases, Kcc4 and Gin4, act redundantly with Hsl1 to regulate Swe1. Kcc4, like Hsl1 and Gin4, was found to localize to the bud neck in a septin-dependent fashion. Interestingly, hsl1 kcc4 gin4 triple mutants develop a cellular morphology extremely similar to that of septin mutants. Consistent with the idea that Hsl1, Kcc4, and Gin4 link entry into mitosis to proper septin organization, we find that septin mutants incubated at the restrictive temperature trigger a Swe1-dependent mitotic delay that is necessary to maintain cell viability. These results reveal for the first time how cells monitor the organization of their cytoskeleton and demonstrate the existence of a cell cycle checkpoint that responds to defects in the peripheral cytoskeleton. Moreover, Hsl1, Kcc4, and Gin4 have homologs in higher eukaryotes, suggesting that the regulation of Swe1/Wee1 by this class of kinases is highly conserved.