Bora and the Kinase Aurora A Cooperatively Activate the Kinase Plk1 and Control Mitotic Entry
Abstract
A central question in the study of cell proliferation is, what controls cell-cycle transitions? Although the accumulation of mitotic cyclins drives the transition from the G2 phase to the M phase in embryonic cells, the trigger for mitotic entry in somatic cells remains unknown. We report that the synergistic action of Bora and the kinase Aurora A (Aur-A) controls the G2-M transition. Bora accumulates in the G2 phase and promotes Aur-A–mediated activation of Polo-like kinase 1 (Plk1), leading to the activation of cyclin-dependent kinase 1 and mitotic entry. Mechanistically, Bora interacts with Plk1 and controls the accessibility of its activation loop for phosphorylation and activation by Aur-A. Thus, Bora and Aur-A control mitotic entry, which provides a mechanism for one of the most important yet ill-defined events in the cell cycle.
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We thank J. Maller (University of Colorado) for baculoviruses expressing Plx1 and its mutants; M. Cyert (Stanford University) for comments on the manuscript; H. Du for technical assistance; and members of the Fang lab for discussions. This work was supported by a Burroughs-Wellcome Career Award in Biomedical Research (G.F.) and grants from NIH (GM062852 to G.F. and HL079442 and RR11823-10 to J.Y.).
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Science
Volume 320 | Issue 5883
20 June 2008
20 June 2008
Copyright
American Association for the Advancement of Science.
Submission history
Received: 6 March 2008
Accepted: 21 May 2008
Published in print: 20 June 2008
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www.sciencemag.org/cgi/content/full/320/5883/1655/DC1
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Figs. S1 to S8
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