Drosophila Wee1 kinase regulates Cdk1 and mitotic entry during embryogenesis.
Cyclin-dependent kinases (Cdks) are the central regulators of the cell division cycle. Inhibitors of Cdks ensure proper coordination of cell cycle events and help regulate cell proliferation in the context of tissues and organs. Wee1 homologs phosphorylate a conserved tyrosine to inhibit the mitotic cyclin-dependent kinase Cdk1. Loss of Wee1 function in fission or budding yeast causes premature entry into mitosis. The importance of metazoan Wee1 homologs for timing mitosis, however, has been demonstrated only in Xenopus egg extracts and via ectopic Cdk1 activation . Here, we report that Drosophila Wee1 (dWee1) regulates Cdk1 via phosphorylation of tyrosine 15 and times mitotic entry during the cortical nuclear cycles of syncytial blastoderm embryos, which lack gap phases. Loss of maternal dwee1 leads to premature entry into mitosis, mitotic spindle defects, chromosome condensation problems, and a Chk2-dependent block of subsequent development, and then embryonic lethality. These findings modify previous models about cell cycle regulation in syncytial embryos and demonstrate that Wee1 kinases can regulate mitotic entry in vivo during metazoan development even in cycles that lack a G2 phase.
Stumpff
Jason
J
Department of Molecular, Cellular, and Developmental Biology, University of Colorado, Boulder, CO 80309-0347, USA.
Duncan
Tod
T
Homola
Ellen
E
Campbell
Shelagh D
SD
Su
Tin Tin
TT
D000818:Animals; D016203:CDC2 Protein Kinase / Q000378:metabolism* / Q000502:physiology; D018797:Cell Cycle Proteins / Q000378:metabolism*; D004330:Drosophila / Q000196:embryology* / Q000502:physiology; D005455:Fluorescent Antibody Technique; D018507:Gene Expression Regulation, Developmental / Q000502:physiology*; D047468:Immunoprecipitation; D018613:Microscopy, Confocal; D008938:Mitosis / Q000502:physiology*; D008954:Models, Biological; D010766:Phosphorylation; D020133:Reverse Transcriptase Polymerase Chain Reaction; D008941:Spindle Apparatus / Q000502:physiology
D018797:Cell Cycle Proteins; D016203:CDC2 Protein Kinase