Journal
CELL CYCLE
Volume 9, Issue 22, Pages 4592-4599Publisher
TAYLOR & FRANCIS INC
DOI: 10.4161/cc.9.22.13665
Keywords
Aurora A; DNA damage; mitosis; TPX2; translation
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Funding
- Krebsliga of the Kanton Zurich
- UBS-Foundation
- Herzog-Egli Foundation
- Hartmann-Muller Foundation
- Novartis Foundation
- University of Zurich
- BBSRC, UK
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We have previously shown that the DNA damage-induced G 2 arrest is contributed by inhibition of Aurora A (AurA) and that transduction of active AurA into arrested cells allows bypassing the block through reactivation of CDK1. In this study, we investigated the mechanism of DNA damage-induced AurA inhibition. We provide evidence that ionizing radiation (IR) administered in mitosis, a time when AurA protein and enzymatic activity reach peak levels, impairs interaction with the partner TPX2, leading to inactivation of the kinase through dephosphorylation of AurA T-loop residue, T-288. We find that decreased AurA-TPX2 complex formation in response to irradiation results from reduced cellular levels of TPX2, an effect that is contributed both by increased APC/CDH1-dependent protein degradation and by decreased translation of TPX2 mRNA.
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