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Cell Cycle. 2013 Apr 1;12(7):1030-41. doi: 10.4161/cc.24004. Epub 2013 Feb 21.

Aurora B prevents delayed DNA replication and premature mitotic exit by repressing p21(Cip1).

Author information

1
Cell Division and Cancer Group, Spanish National Cancer Research Centre (CNIO), Madrid, Spain.

Abstract

Aurora kinase B is a critical component of the chromosomal passenger complex, which is involved in the regulation of microtubule-kinetochore attachments and cytokinesis. By using conditional knockout cells and chemical inhibition, we show here that inactivation of Aurora B results in delayed G(1)/S transition and premature mitotic exit. Aurora B deficiency results in delayed DNA replication in cultured fibroblasts as well as liver cells after hepatectomy. This is accompanied by increased transcription of the cell cycle inhibitor p21 (Cip1). Lack of Aurora B does not prevent mitotic entry but results in a premature exit from prometaphase in the presence of increased p21(Cip1)-Cdk1 inactive complexes. Aurora B-null cells display reduced degradation of cyclin B1, suggesting the presence of phenomenon known as adaptation to the mitotic checkpoint, previously described in yeast. Elimination of p21(Cip1) rescues Cdk1 activity and prevents premature mitotic exit in Aurora B-deficient cells. These results suggest that Aurora B represses p21(Cip1), preventing delayed DNA replication, Cdk inhibition and premature mitotic exit. The upregulation of p21(Cip1) observed after inhibition of Aurora B may have important implications in cell cycle progression, tetraploidy, senescence or cancer therapy.

KEYWORDS:

Aurora kinase B; G1/S progression; cancer target; mitosis; spindle assembly checkpoint

PMID:
23428904
PMCID:
PMC3646860
DOI:
10.4161/cc.24004
[Indexed for MEDLINE]
Free PMC Article

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