Phosphate-binding pocket on cyclin B governs CDK substrate phosphorylation and mitotic timing.
Phosphate-binding pocket on cyclin B governs CDK substrate phosphorylation and mitotic timing.
复制标题
细胞周期蛋白 B 上的磷酸盐结合袋控制 CDK 底物磷酸化和有丝分裂计时。
DOI：
10.1101/2024.02.28.582599
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发表时间：
2024
期刊：
影响因子：
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通讯作者：
Morgan,DavidO
中科院分区：
文献类型：
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作者：
Ng,HenryY;Adly,ArminN;Whelpley,DevonH;Suhandynata,RaymondT;Zhou,Huilin;Morgan,DavidO
细胞周期进程由细胞周期蛋白依赖性激酶（CDKs）及其调节亚基cyclin和Cks 1的复合物控制。CDK通常在多个位点磷酸化数百种底物。多位点磷酸化依赖于Cks 1，其结合初始引发磷酸化位点以促进其他位点的二次磷酸化。在这里，我们描述了一个类似的作用，最近发现的磷酸结合口袋（PP）的B型细胞周期蛋白。芽殖酵母的主要有丝分裂细胞周期蛋白Clb 2中PP的突变改变芽的形态并延迟后期的开始。PP的突变减少了体外CDK底物的多位点磷酸化，包括后期促进复合物/细胞周期体的Cdc 16和Cdc 27亚基以及极化体的Bud 6和Spa 2亚基。我们的结论是，细胞周期蛋白PP，Cks 1一样，控制CDK底物上的多位点磷酸化的模式，从而有助于建立强大的细胞周期事件的时间。
Cell cycle progression is governed by complexes of the cyclin-dependent kinases (CDKs) and their regulatory subunits cyclin and Cks1. CDKs phosphorylate hundreds of substrates, often at multiple sites. Multisite phosphorylation depends on Cks1, which binds initial priming phosphorylation sites to promote secondary phosphorylation at other sites. Here, we describe a similar role for a recently discovered phosphate-binding pocket (PP) on B-type cyclins. Mutation of the PP in Clb2, the major mitotic cyclin of budding yeast, alters bud morphology and delays the onset of anaphase. Mutation of the PP reduces multi-site phosphorylation of CDK substrates in vitro, including the Cdc16 and Cdc27 subunits of the anaphase-promoting complex/cyclosome and the Bud6 and Spa2 subunits of the polarisome. We conclude that the cyclin PP, like Cks1, controls the pattern of multisite phosphorylation on CDK substrates, thereby helping to establish the robust timing of cell-cycle events.