Abstract
Cyclin B1 is a key regulatory protein controlling cell cycle progression in vertebrates. Cyclin B1 binds CDK1, a cyclin-dependent kinase catalytic subunit, forming a complex that orchestrates mitosis through phosphorylation of key proteins. Cyclin B1 regulates both the activation of CDK1 and its subcellular localization, which may be critical for substrate selection. Here, we demonstrate that cyclin B1 is concentrated on the outer plate of the kinetochore during prometaphase. This localization requires the cyclin box region of the protein. Cyclin B1 is displaced from individual kinetochores to the spindle poles by microtubule attachment to the kinetochores, and this displacement is dependent on the dynein/dynactin complex. Depletion of cyclin B1 by vector-based siRNA causes inefficient attachment between kinetochores and microtubules, and chromosome alignment defects, and delays the onset of anaphase. We conclude that cyclin B1 accumulates at kinetochores during prometaphase, where it contributes to the correct attachment of microtubules to kinetochores and efficient alignment of the chromosomes, most likely through localized phosphorylation of specific substrates by cyclin B1-CDK1. Cyclin B1 is then transported from each kinetochore as microtubule attachment is completed, and this relocalization may redirect the activity of cyclin B1-CDK1 and contribute to inactivation of the spindle assembly checkpoint.
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Acknowledgements
We gratefully thank all the other members in our laboratories for useful comments. This work was supported by funds from the National Natural Science Foundation of China (NSFC) (30421004, 30225016, 30330200 and 30671063), the National Basic Research Program of China (2004CB720003 and 2006CB0D0100) and the National Key Scientific Program of China (2007CB914502). PRC is the holder of a Royal Society-Wolfson Research Merit Award.
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Chen, Q., Zhang, X., Jiang, Q. et al. Cyclin B1 is localized to unattached kinetochores and contributes to efficient microtubule attachment and proper chromosome alignment during mitosis. Cell Res 18, 268–280 (2008). https://doi.org/10.1038/cr.2008.11
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DOI: https://doi.org/10.1038/cr.2008.11
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