Genome-wide survey of protein kinases required for cell cycle progression

Genome-wide survey of protein kinases required for cell cycle progression
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DOI:
10.1038/nature03160
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发表时间:
2004-12-23
期刊:
影响因子:
64.8
通讯作者:
Glover, DM
Glover, DM
中科院分区:
综合性期刊1区
文献类型:
--
作者:
Bettencourt-Dias, M;Giet, R;Glover, DM

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蛋白质磷酸化周期是真核细胞分裂周期中调节细胞进程的基础。在这里,我们测试了果蝇蛋白激酶(kinome)补体在rna介导的干扰下基因沉默后的细胞周期功能。我们观察到228种蛋白激酶中的80种下调细胞周期功能障碍,包括大多数已知调节分裂周期的激酶。我们发现了具有细胞周期功能的新酶;其中一些有已知的家族成员磷酸化微管,肌动蛋白或其相关蛋白。此外,一些信号激酶的耗竭会导致特定的有丝分裂畸变,这表明熟悉的酶具有新的作用。该调查揭示了监测细胞生理、细胞大小、细胞应激和信号传导过程的系统与基本细胞周期调节机制的相互数字化。
Cycles of protein phosphorylation are fundamental in regulating the progression of the eukaryotic cell through its division cycle. Here we test the complement of Drosophila protein kinases (kinome) for cell cycle functions after gene silencing by RNA-mediated interference. We observed cell cycle dysfunction upon downregulation of 80 out of 228 protein kinases, including most kinases that are known to regulate the division cycle. We find new enzymes with cell cycle functions; some of these have family members already known to phosphorylate microtubules, actin or their associated proteins. Additionally, depletion of several signalling kinases leads to specificmitotic aberrations, suggesting novel roles for familiar enzymes. The survey reveals the inter-digitation of systems that monitor cellular physiology, cell size, cellular stress and signalling processes with the basic cell cycle regulatory machinery.