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Published December 23, 2004 | Supplemental Material
Journal Article Open

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

Abstract

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.

Additional Information

© 2004 Nature Publishing Group. Received 02 July 2004. Accepted 28 October 2004. Issue Date 23 December 2004. We thank Cancer Research UK and BBSRC for supporting work in the CR-UK Cell Cycle Genetics Research Group. The BBSRC support was part of a LINK Programme in which the Department of Trade and Industry also provide support for Cyclacel Ltd. An NIH grant supported work in R.W.C.'s group and JSPS funded S.Y. We thank N. B. Carmo, C. Malone and N. Miller for help with experiments. We are grateful to J. C. Pezzullo for his expertise with excel statistical macros and to F. Scaerou, C. Midgley and J. Pereira-Leal for discussions. We also thank T. Hunt, J. Maller and our colleagues, particularly A. Carpenter, M. Segal and M. Savoian for their comments on the manuscript. The authors declare that they have no competing financial interests.

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