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Published online
doi:10.1083/jcb.200710019
The Journal of Cell Biology, Vol. 181, No. 2, 241-254
The Rockefeller University Press, 0021-9525 $30.00
© Emanuele et al.
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Article

Aurora B kinase and protein phosphatase 1 have opposing roles in modulating kinetochore assembly



Michael J. Emanuele1, Weijie Lan1, Miri Jwa2, Stephanie A. Miller1, Clarence S.M. Chan2, and P. Todd Stukenberg1

1 Department of Biochemistry and Molecular Genetics, University of Virginia, Charlottesville, VA 22908
2 Section of Molecular Genetics and Microbiology, Institute for Cellular and Molecular Biology, The University of Texas, Austin, TX 78712

Correspondence to P.T. Stukenberg: pts7h{at}virginia.edu

The outer kinetochore binds microtubules to control chromosome movement. Outer kinetochore assembly is restricted to mitosis, whereas the inner kinetochore remains tethered to centromeres throughout the cell cycle. The cues that regulate this transient assembly are unknown. We find that inhibition of Aurora B kinase significantly reduces outer kinetochore assembly in Xenopus laevis and human tissue culture cells, frog egg extracts, and budding yeast. In X. leavis M phase extracts, preassembled kinetochores disassemble after inhibiting Aurora B activity with either drugs or antibodies. Kinetochore disassembly, induced by Aurora B inhibition, is rescued by restraining protein phosphatase 1 (PP1) activity. PP1 is necessary for kinetochores to disassemble at the exit from M phase, and purified enzyme is sufficient to cause disassembly on isolated mitotic nuclei. These data demonstrate that Aurora B activity is required for kinetochore maintenance and that PP1 is necessary and sufficient to disassemble kinetochores. We suggest that Aurora B and PP1 coordinate cell cycle–dependent changes in kinetochore assembly though phosphorylation of kinetochore substrates.

Abbreviations used in this paper: ACA, anti-centromere antigen; Cenp, centromere protein; ChIP, chromatin immunoprecipitation; CSF, cytostatic factor; I-2, Inhibitor-2; INCENP, inner centromere protein; PP1, protein phosphatase 1.


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