FoxM1 is required for execution of the mitotic programme and chromosome stability.
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.
Laoukili
Jamila
J
Division of Molecular Biology, Netherlands Cancer Institute, Plesmanlaan 121, 1066 CX Amsterdam, The Netherlands.
Kooistra
Matthijs R H
MR
Brás
Alexandra
A
Kauw
Jos
J
Kerkhoven
Ron M
RM
Morrison
Ashby
A
Clevers
Hans
H
Medema
René H
RH
D000818:Animals; D002453:Cell Cycle; D043171:Chromosomal Instability; D002868:Chromosomal Proteins, Non-Histone / Q000502:physiology; D020090:Chromosome Segregation; D019926:Cyclin B / Q000378:metabolism; D056744:Cyclin B1; D004268:DNA-Binding Proteins / Q000502:physiology; D000072278:Forkhead Box Protein M1; D051858:Forkhead Transcription Factors; D005786:Gene Expression Regulation; D006801:Humans; D051379:Mice; D008840:Microfilament Proteins; D008938:Mitosis; D014157:Transcription Factors / Q000502:physiology*
C534699:CCNB1 protein, human; C534700:Ccnb1 protein, mouse; D002868:Chromosomal Proteins, Non-Histone; D019926:Cyclin B; D056744:Cyclin B1; D004268:DNA-Binding Proteins; D000072278:Forkhead Box Protein M1; D051858:Forkhead Transcription Factors; C491524:Foxm1 protein, mouse; D008840:Microfilament Proteins; D014157:Transcription Factors; C094772:centromere protein F