Laoukili Jamila, Kooistra Matthijs R H, Brás Alexandra, Kauw Jos, Kerkhoven Ron M, Morrison Ashby, Clevers Hans, Medema René H
Division of Molecular Biology, Netherlands Cancer Institute, Plesmanlaan 121, 1066 CX Amsterdam, The Netherlands.
Nat Cell Biol. 2005 Feb;7(2):126-36. doi: 10.1038/ncb1217. Epub 2005 Jan 16.
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.
细胞周期调节蛋白的转录诱导确保了后续细胞周期事件的正确时间安排。我们在此表明，叉头转录因子FoxM1调节许多G2期特异性基因的表达，并且对于染色体稳定性至关重要。FoxM1的缺失会导致多效性细胞周期缺陷，包括G2期延迟、染色体错分离和频繁的胞质分裂失败。我们表明，FoxM1对细胞周期蛋白B的转录激活对于及时进入有丝分裂至关重要，而CENP-F（此处鉴定出的FoxM1的另一个直接靶点）对于有丝分裂纺锤体检查点的精确功能至关重要。因此，我们的数据揭示了一个由FoxM1调节的转录簇，该转录簇对于正确的有丝分裂进程至关重要。
