Abstract
Transcriptional induction of cell-cycle regulatory proteins ensures proper timing of subsequent cell-cycle events. Here we show that the Forkhead transcription factor FoxM1 regulates expression of many G2-specific genes and is essential for chromosome stability. Loss of FoxM1 leads to pleiotropic cell-cycle defects, including a delay in G2, chromosome mis-segregation and frequent failure of cytokinesis. We show that transcriptional activation of cyclin B by FoxM1 is essential for timely mitotic entry, whereas CENP-F, another direct target of FoxM1 identified here, is essential for precise functioning of the mitotic spindle checkpoint. Thus, our data uncover a transcriptional cluster regulated by FoxM1 that is essential for proper mitotic progression.
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Acknowledgements
We would like to thank the other members of the laboratory for helpful discussions and daily support. We would also like to thank M. Heimerikx and A. Velds for expert technical assistance with microarray analyses, R. Beijersbergen for the retro-pSuper-CENP-F, S. Taylor for the anti-BubR1 antibody and helpful discussion, R. Herrera for help with ChIP assays, and L. Oomen and L. Brocks for support with confocal microscopy. The authors acknowledge support from the Dutch Cancer Society and from the FCT (to A.B).
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Laoukili, J., Kooistra, M., Brás, A. et al. FoxM1 is required for execution of the mitotic programme and chromosome stability. Nat Cell Biol 7, 126–136 (2005). https://doi.org/10.1038/ncb1217
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DOI: https://doi.org/10.1038/ncb1217
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