DOI: 10.1126/science.1167000. Sensing Chromosome Bi-Orientation by Spatial Separation of Aurora B Kinase from Kinetochore Substrates [Penn]

Sensing Chromosome Bi-Orientation by Spatial Separation of Aurora B Kinase from Kinetochore Substrates

10.1126/science.1167000

Crossref journal-article

American Association for the Advancement of Science (AAAS)

Science (221)

Abstract

Successful cell division requires that chromosomes attach to opposite poles of the mitotic spindle (bi-orientation). Aurora B kinase regulates chromosome-spindle attachments by phosphorylating kinetochore substrates that bind microtubules. Centromere tension stabilizes bi-oriented attachments, but how physical forces are translated into signaling at individual centromeres is unknown. Using fluorescence resonance energy transfer–based biosensors to measure localized phosphorylation dynamics in living cells, we found that phosphorylation of an Aurora B substrate at the kinetochore depended on its distance from the kinase at the inner centromere. Furthermore, repositioning Aurora B closer to the kinetochore prevented stabilization of bi-oriented attachments and activated the spindle checkpoint. Thus, centromere tension can be sensed by increased spatial separation of Aurora B from kinetochore substrates, which reduces phosphorylation and stabilizes kinetochore microtubules.

Bibliography

Liu, D., Vader, G., Vromans, M. J. M., Lampson, M. A., & Lens, S. M. A. (2009). Sensing Chromosome Bi-Orientation by Spatial Separation of Aurora B Kinase from Kinetochore Substrates. Science, 323(5919), 1350â1353.

Authors 5

Dan Liu (first)
Gerben Vader (additional)
Martijn J. M. Vromans (additional)
Michael A. Lampson (additional)
Susanne M. A. Lens (additional)

References 25 Referenced 473

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We thank T. M. Kapoor (Rockefeller University) and R. H. Medema (University Medical Center Utrecht) for their support during the initiation of these studies. We also thank B. E. Black G. Kops and R. H. Medema for critical reading of the manuscript and helpful comments and K. V. Le and T. Chiang for assistance with preparing reagents. This work was supported by grants from the American Cancer Society (IRG-78-002-30 M.A.L.) the National Institutes of Health (GM083988 M.A.L.) the Searle Scholars Program (M.A.L.) the Penn Genome Frontiers Institute (M.A.L.) and the Netherlands Organization for Scientific Research (Vidi 917.66.332 S.M.A.L.).

Dates

Type	When
Created	16 years, 7 months ago (Jan. 15, 2009, 9:54 p.m.)
Deposited	1 year, 7 months ago (Jan. 10, 2024, 4:21 a.m.)
Indexed	5 days, 10 hours ago (Aug. 21, 2025, 2:21 p.m.)
Issued	16 years, 5 months ago (March 6, 2009)
Published	16 years, 5 months ago (March 6, 2009)
Published Print	16 years, 5 months ago (March 6, 2009)

Funders 0

None

BibTeX

@article{Liu_2009, title={Sensing Chromosome Bi-Orientation by Spatial Separation of Aurora B Kinase from Kinetochore Substrates}, volume={323}, ISSN={1095-9203}, url={http://dx.doi.org/10.1126/science.1167000}, DOI={10.1126/science.1167000}, number={5919}, journal={Science}, publisher={American Association for the Advancement of Science (AAAS)}, author={Liu, Dan and Vader, Gerben and Vromans, Martijn J. M. and Lampson, Michael A. and Lens, Susanne M. A.}, year={2009}, month=mar, pages={1350–1353} }

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