Nature Cell Biology
7, 126 - 136 (2005)
Published online: 16 January 2005; | doi:10.1038/ncb1217
FoxM1 is required for execution of the mitotic programme and chromosome stabilityJamila Laoukili1, Matthijs R. H. Kooistra1, Alexandra Brás1, Jos Kauw1, Ron M. Kerkhoven2, Ashby Morrison3, Hans Clevers4
& René H. Medema11
Division of Molecular Biology, Netherlands Cancer Institute, Plesmanlaan 121, 1066 CX Amsterdam, The Netherlands. 2
Division of Molecular Carcinogenesis, Netherlands Cancer Institute, Plesmanlaan 121, 1066 CX Amsterdam, The Netherlands. 3
Department of Molecular and Cellular Biology, Baylor College of Medicine, Houston, TX 77030, USA. 4
Hubrecht Laboratory, Netherlands Institute for Developmental Biology, Uppsalalaan 8, 3584 CT Utrecht, The Netherlands.
Correspondence should be addressed to René H. Medema r.medema@nki.nlTranscriptional 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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