Evidence that Aurora B is implicated in spindle checkpoint signalling independently of error correction

被引:160
作者
Santaguida, Stefano [1 ]
Vernieri, Claudio [2 ]
Villa, Fabrizio [1 ]
Ciliberto, Andrea [2 ]
Musacchio, Andrea [1 ,3 ]
机构
[1] European Inst Oncol, Dept Expt Oncol, I-20139 Milan, Italy
[2] FIRC Inst Mol Oncol, Milan, Italy
[3] Max Planck Inst Mol Physiol, Dept Mechanist Cell Biol, D-44139 Dortmund, Germany
基金
欧洲研究理事会;
关键词
centromere; hesperadin; kinetochore; reversine; tension; KINETOCHORE-MICROTUBULE INTERFACE; ASSEMBLY CHECKPOINT; CHROMOSOME SEGREGATION; MITOTIC CHECKPOINT; BUDDING YEAST; HUMAN-CELLS; KINASE; COMPLEX; TENSION; INHIBITORS;
D O I
10.1038/emboj.2011.70
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Fidelity of chromosome segregation is ensured by a tension-dependent error correction system that prevents stabilization of incorrect chromosome-microtubule attachments. Unattached or incorrectly attached chromosomes also activate the spindle assembly checkpoint, thus delaying mitotic exit until all chromosomes are bioriented. The Aurora B kinase is widely recognized as a component of error correction. Conversely, its role in the checkpoint is controversial. Here, we report an analysis of the role of Aurora B in the spindle checkpoint under conditions believed to uncouple the effects of Aurora B inhibition on the checkpoint from those on error correction. Partial inhibition of several checkpoint and kinetochore components, including Mps1 and Ndc80, strongly synergizes with inhibition of Aurora B activity and dramatically affects the ability of cells to arrest in mitosis in the presence of spindle poisons. Thus, Aurora B might contribute to spindle checkpoint signalling independently of error correction. Our results support a model in which Aurora B is at the apex of a signalling pyramid whose sensory apparatus promotes the concomitant activation of error correction and checkpoint signalling pathways. The EMBO Journal (2011) 30, 1508-1519. doi:10.1038/emboj.2011.70; Published online 15 March 2011 Subject Categories: cell cycle
引用
收藏
页码:1508 / 1519
页数:12
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