Bettencourt-Dias M, Giet R, Sinka R, Mazumdar A, Lock W G, Balloux F, Zafiropoulos P J, Yamaguchi S, Winter S, Carthew R W, Cooper M, Jones D, Frenz L, Glover D M
Cancer Research UK Cell Cycle Genetics Research Group, University of Cambridge, Department of Genetics, Downing Street, Cambridge CB2 3EH, UK.
Nature. 2004 Dec 23;432(7020):980-7. doi: 10.1038/nature03160.
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 specific mitotic 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.
蛋白质磷酸化循环在调节真核细胞通过其分裂周期的进程中起着基础性作用。在这里,我们通过RNA介导的干扰使基因沉默后,测试了果蝇蛋白激酶(激酶组)对细胞周期功能的补充作用。我们观察到,在228种蛋白激酶中有80种下调后出现了细胞周期功能障碍,其中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;其中一些酶有已知能磷酸化微管、肌动蛋白或其相关蛋白的家族成员。此外,几种信号激酶的缺失会导致特定的有丝分裂异常,这表明一些常见酶有新的作用。这项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之间的相互交织。