DOI: 10.1083/jcb.200208091. Aurora B couples chromosome alignment with anaphase by targeting BubR1, Mad2, and Cenp-E to kinetochores

Aurora B couples chromosome alignment with anaphase by targeting BubR1, Mad2, and Cenp-E to kinetochores

10.1083/jcb.200208091

Crossref journal-article

Rockefeller University Press

The Journal of Cell Biology (291)

Abstract

The Aurora/Ipl1 family of protein kinases plays multiple roles in mitosis and cytokinesis. Here, we describe ZM447439, a novel selective Aurora kinase inhibitor. Cells treated with ZM447439 progress through interphase, enter mitosis normally, and assemble bipolar spindles. However, chromosome alignment, segregation, and cytokinesis all fail. Despite the presence of maloriented chromosomes, ZM447439-treated cells exit mitosis with normal kinetics, indicating that the spindle checkpoint is compromised. Indeed, ZM447439 prevents mitotic arrest after exposure to paclitaxel. RNA interference experiments suggest that these phenotypes are due to inhibition of Aurora B, not Aurora A or some other kinase. In the absence of Aurora B function, kinetochore localization of the spindle checkpoint components BubR1, Mad2, and Cenp-E is diminished. Furthermore, inhibition of Aurora B kinase activity prevents the rebinding of BubR1 to metaphase kinetochores after a reduction in centromeric tension. Aurora B kinase activity is also required for phosphorylation of BubR1 on entry into mitosis. Finally, we show that BubR1 is not only required for spindle checkpoint function, but is also required for chromosome alignment. Together, these results suggest that by targeting checkpoint proteins to kinetochores, Aurora B couples chromosome alignment with anaphase onset.

Bibliography

Ditchfield, C., Johnson, V. L., Tighe, A., Ellston, R., Haworth, C., Johnson, T., Mortlock, A., Keen, N., & Taylor, S. S. (2003). Aurora B couples chromosome alignment with anaphase by targeting BubR1, Mad2, and Cenp-E to kinetochores. The Journal of Cell Biology, 161(2), 267â280.

Authors 9

Claire Ditchfield (first)
Victoria L. Johnson (additional)
Anthony Tighe (additional)
Rebecca Ellston (additional)
Carolyn Haworth (additional)
Trevor Johnson (additional)
Andrew Mortlock (additional)
Nicholas Keen (additional)
Stephen S. Taylor (additional)

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Dates

Type	When
Created	22 years, 4 months ago (April 28, 2003, 3:44 p.m.)
Deposited	2 years, 1 month ago (July 22, 2023, 10:15 a.m.)
Indexed	3 days ago (Aug. 31, 2025, 6:08 a.m.)
Issued	22 years, 4 months ago (April 28, 2003)
Published	22 years, 4 months ago (April 28, 2003)
Published Online	22 years, 4 months ago (April 28, 2003)
Published Print	22 years, 4 months ago (April 28, 2003)

Funders 0

None

BibTeX

@article{Ditchfield_2003, title={Aurora B couples chromosome alignment with anaphase by targeting BubR1, Mad2, and Cenp-E to kinetochores}, volume={161}, ISSN={0021-9525}, url={http://dx.doi.org/10.1083/jcb.200208091}, DOI={10.1083/jcb.200208091}, number={2}, journal={The Journal of Cell Biology}, publisher={Rockefeller University Press}, author={Ditchfield, Claire and Johnson, Victoria L. and Tighe, Anthony and Ellston, Rebecca and Haworth, Carolyn and Johnson, Trevor and Mortlock, Andrew and Keen, Nicholas and Taylor, Stephen S.}, year={2003}, month=apr, pages={267–280} }

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