Genome-wide survey of protein kinases required for cell cycle progression.
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.
Bettencourt-Dias
M
M
Cancer Research UK Cell Cycle Genetics Research Group, University of Cambridge, Department of Genetics, Downing Street, Cambridge CB2 3EH, UK. mbcd2@cam.ac.uk
Giet
R
R
Sinka
R
R
Mazumdar
A
A
Lock
W G
WG
Balloux
F
F
Zafiropoulos
P J
PJ
Yamaguchi
S
S
Winter
S
S
Carthew
R W
RW
Cooper
M
M
Jones
D
D
Frenz
L
L
Glover
D M
DM
D000091162:AMP-Activated Protein Kinase Kinases; D000818:Animals; D002453:Cell Cycle / Q000235:genetics / Q000502:physiology*; D049109:Cell Proliferation; D048749:Cytokinesis; D029721:Drosophila Proteins / Q000235:genetics / Q000378:metabolism; D004331:Drosophila melanogaster / Q000166:cytology* / Q000201:enzymology* / Q000235:genetics; D016195:G2 Phase; D016678:Genome; D023281:Genomics; D008938:Mitosis / Q000502:physiology; D009154:Mutation / Q000235:genetics; D009752:Nutritional Status; D011494:Protein Kinases / Q000235:genetics / Q000378:metabolism*; D034622:RNA Interference; D016196:S Phase; D015398:Signal Transduction; D008941:Spindle Apparatus / Q000502:physiology; D013312:Stress, Physiological / Q000235:genetics / Q000503:physiopathology
D029721:Drosophila Proteins; D011494:Protein Kinases; C495775:LKB1 protein, Drosophila; D000091162:AMP-Activated Protein Kinase Kinases