FoxM1 is required for execution of the mitotic programme and chromosome stability

FoxM1 is required for execution of the mitotic programme and chromosome stability
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DOI:
10.1038/ncb1217
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发表时间:
2005-02-01
影响因子:
21.3
通讯作者:
Medema, RH
Medema, RH
中科院分区:
生物学1区
文献类型:
--
作者:
Laoukili, J;Kooistra, MRH;Medema, RH

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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适当时机。在这里,我们证明了Forkhead转录因子FOXM1调节许多G2特异基因的表达,并且对于染色体的稳定性是必不可少的。FOXM1的缺失会导致多效性细胞周期缺陷,包括G2期延迟、染色体错误分离和细胞质分裂频繁失败。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是必不可少的,而CENP-F,这里发现的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是必不可少的。因此,我们的数据揭示了由FOXM1调控的转录簇,这对于正常的有丝分裂进程是必不可少的。
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.