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首页> 外文期刊>Proceedings of the National Academy of Sciences of the United States of America >Temporal Control Of The Dephosphorylation Of Cdk Substrates By Mitotic Exit Pathways In Budding Yeast
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Temporal Control Of The Dephosphorylation Of Cdk Substrates By Mitotic Exit Pathways In Budding Yeast

机译:芽胞酵母中有丝分裂出口通道对Cdk底物去磷酸化的时间控制

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摘要

The temporal phosphorylation of cell cycle-related proteins by cyclin-dependent kinases (Cdks) is critical for the correct order of cell cycle events. In budding yeast, CDC28 encodes the only Cdk and its association with various cyclins governs the temporal phosphorylation of Cdk substrates. S-phase Cdk substrates are phos-phorylated earlier than mitotic Cdk substrates, which ensures the sequential order of DNA synthesis and mitosis. However, it remains unclear whether Cdk substrates are dephosphorylated in temporally distinct windows. Cdc14 is a conserved protein phosphatase responsible for the dephosphorylation of Cdk substrates. In budding yeast, FEAR (Cdc14 early anaphase release) and MEN (mitotic exit network) activate phosphatase Cdc14 by promoting its release from the nucleolus in early and late anaphase, respectively. Here, we show that the sequential Cdc14 release and the distinct degradation timing of different cyclins provides the molecular basis for the differential dephosphorylation windows of S-phase and mitotic cyclin substrates. Our data also indicate that FEAR-induced dephosphorylation of S-phase Cdk substrates facilitates anaphase progression, revealing an extra layer of mitotic regulation.
机译:细胞周期蛋白依赖性激酶(Cdks)对细胞周期相关蛋白的时间磷酸化对于细胞周期事件的正确顺序至关重要。在发芽酵母中,CDC28编码唯一的Cdk,其与各种细胞周期蛋白的结合决定了Cdk底物的暂时磷酸化。 S期Cdk底物比有丝分裂Cdk底物更早被磷酸化,这确保了DNA合成和有丝分裂的顺序。但是,尚不清楚Cdk底物是否在时间上不同的窗口中被去磷酸化。 Cdc14是保守的蛋白质磷酸酶,负责Cdk底物的去磷酸化。在发芽酵母中,FEAR(Cdc14后期早期释放)和MEN(有丝分裂出口网络)通过促进磷酸酶Cdc14分别在后期早期和后期从核仁中释放来激活磷酸酶。在这里,我们表明Cdc14的顺序释放和不同细胞周期蛋白的独特降解时机为S期和有丝分裂细胞周期蛋白底物的差异去磷酸化窗口提供了分子基础。我们的数据还表明,FEAR诱导的S期Cdk底物的去磷酸化促进了后期的进程,揭示了有丝分裂调控的另一层。

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