Concerted mechanism of Swe1/Wee1 regulation by multiple kinases in budding yeast
Concerted mechanism of Swe1/Wee1 regulation by multiple kinases in budding yeast
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DOI：
10.1038/sj.emboj.7600683
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发表时间：
2005-06-15
期刊：
影响因子：
11.4
通讯作者：
Lee, KS
中科院分区：
文献类型：
--
作者：
Asano, S;Park, JE;Lee, KS
在真核生物中，细胞周期蛋白B结合的Cdk1诱导进入有丝分裂，而它受到蛋白激酶Wee1的抑制。在出芽酵母中，Swe1（Wee1的同源物）通过Hsl1（与Nim1相关的激酶）及其衔接蛋白Hsl7靶向芽颈，并在泛素介导的降解之前被过度磷酸化。在此，我们表明Hsl1和Hsl7是Cdc5（类Polo激酶同源物）正确定位到芽颈以及Cdc5依赖的Swe1磷酸化所必需的。有丝分裂细胞周期蛋白（Clb2）结合的Cdc28（Cdk1同源物）直接磷酸化Swe1，这种修饰作为一个起始步骤，促进随后Cdc5依赖的Swe1过度磷酸化和降解。Clb2 - Cdc28还通过增强Clb2 - Cdc28磷酸化的Swe1与Cdc5的Polo盒结构域之间的相互作用，促进Cdc5定位到芽颈。我们提出，Cdc28/Cdk1和Cdc5/Polo对它们共同底物的协同作用是一种在进化上保守的机制，对于有效触发有丝分裂进入和其他关键的有丝分裂事件至关重要。
In eukaryotes, entry into mitosis is induced by cyclin B-bound Cdk1 which is held in check by the protein kinase, Wee1. In budding yeast, Swe1 (Wee1 ortholog) is targeted to the bud neck through Hsl1 (Nim1-related kinase) and its adaptor Hsl7, and is hyperphosphorylated prior to ubiquitin-mediated degradation. Here, we show that Hsl1 and Hsl7 are required for proper localization of Cdc5 (Polo-like kinase homolog) to the bud neck and Cdc5-dependent Swe1 phosphorylation. Mitotic cyclin (Clb2)-bound Cdc28 (Cdk1 homolog) directly phosphorylated Swe1 and this modification served as a priming step to promote subsequent Cdc5-dependent Swe1 hyperphosphorylation and degradation. Clb2-Cdc28 also facilitated Cdc5 localization to the bud neck through the enhanced interaction between the Clb2-Cdc28-phosphorylated Swe1 and the polo-box domain of Cdc5. We propose that the concerted action of Cdc28/Cdk1 and Cdc5/Polo on their common substrates is an evolutionarily conserved mechanism that is crucial for effectively triggering mitotic entry and other critical mitotic events.