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Bora and the Kinase Aurora A Cooperatively Activate the Kinase Plk1 and Control Mitotic Entry

Science
20 Jun 2008
Vol 320, Issue 5883
pp. 1655-1658

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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Published In

Science
Volume 320 | Issue 5883
20 June 2008

Submission history

Received: 6 March 2008
Accepted: 21 May 2008
Published in print: 20 June 2008

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Notes

Supporting Online Material
www.sciencemag.org/cgi/content/full/320/5883/1655/DC1
Materials and Methods
Figs. S1 to S8
References

Authors

Affiliations

Akiko Seki
Department of Biological Sciences, Stanford University, Stanford, CA 94305–5020, USA.
Judith A. Coppinger
Department of Chemical Physiology, The Scripps Research Institute, La Jolla, CA 92037, USA.
Chang-Young Jang
Department of Biological Sciences, Stanford University, Stanford, CA 94305–5020, USA.
John R. Yates, III
Department of Chemical Physiology, The Scripps Research Institute, La Jolla, CA 92037, USA.
Guowei Fang*
Department of Biological Sciences, Stanford University, Stanford, CA 94305–5020, USA.

Notes

*
To whom correspondence should be addressed. E-mail: [email protected]

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