期刊
NATURE COMMUNICATIONS
卷 6, 期 -, 页码 -出版社
NATURE PUBLISHING GROUP
DOI: 10.1038/ncomms7891
关键词
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资金
- D-A-CH initiative from Austrian Science Fund (FWF)
- Deutsche Forschungsgemeinschaft (DFG) (FOR-2036) [I1298]
- Tyrolean Science Fund (TWF)
- Krebshilfe Tirol
- EMBO-LTF program
- Austrian Science Fund (FWF) [I 1298] Funding Source: researchfish
- Austrian Science Fund (FWF) [I1298] Funding Source: Austrian Science Fund (FWF)
Cell death on extended mitotic arrest is considered arguably most critical for the efficacy of microtubule-targeting agents (MTAs) in anticancer therapy. While the molecular machinery controlling mitotic arrest on MTA treatment, the spindle assembly checkpoint (SAC), appears well defined, the molecular components executing cell death, as well as factors connecting both networks remain poorly understood. Here we conduct a mini screen exploring systematically the contribution of individual BCL2 family proteins at single cell resolution to death on extended mitotic arrest, and demonstrate that the mitotic phosphorylation of BCL2 and BCLX represent a priming event for apoptosis that is ultimately triggered by NOXA-dependent MCL1 degradation, enabling BIM-dependent cell death. Our findings provide a comprehensive model for the initiation of apoptosis in cells stalled in mitosis and provide a molecular basis for the increased efficacy of combinatorial treatment of cancer cells using MTAs and BH3 mimetics.
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