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Co-regulation of the antagonistic RepoMan:Aurora-B pair in proliferating cells

阿平添加于 2020-1-28 22:43 | 904 次阅读 | 0 个评论

作者
Manzione MG, Rombouts J, Steklov M, Pasquali L, Sablina A, Gelens L, Qian J, Bollen M
摘要
Chromosome segregation during mitosis is antagonistically regulated by the Aurora-B kinase and RepoMan-associated phosphatases PP1/PP2A. Aurora B is overexpressed in many cancers but, surprisingly, this only rarely causes lethal aneuploidy. Here we show that RepoMan abundance is regulated by the same mechanisms that control Aurora B, including FOXM1-regulated expression and proteasomal degradation following ubiquitination by APC/C-CDH1 or SCF/FBXW7. The deregulation of these mechanisms can account for the balanced co-overexpression of Aurora B and RepoMan in many cancers, which limits chromosome segregation errors. In addition, Aurora B and RepoMan independently promote cancer cell proliferation by reducing checkpoint-induced cell-cycle arrest during interphase. The co-upregulation of RepoMan and Aurora B in tumors is inversely correlated with patient survival, underscoring its potential importance for tumor progression. Finally, we demonstrate that high RepoMan levels sensitize cancer cells to Aurora-B inhibitors. Hence, the co-upregulation of RepoMan and Aurora B is associated with tumor aggressiveness but also exposes a vulnerable target for therapeutic intervention.
详细资料
- 文献种类:期刊
- 期刊名称: Molecular Biology of the Cell
- 期刊缩写: Mol Biol Cell
- 期卷页: 2020年 mbcE19120698页
- 地址: Laboratory of Biosignaling & Therapeutics
- ISBN: 1059-1524
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