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Mitotic DNA damage targets the Aurora A/TPX2 complex
journal contribution
posted on 2023-06-08, 05:04 authored by Payal Bhatia, Mirco Menigatti, Michele Brocard, Simon Morley, Stefano FerrariWe have previously shown that the DNA damage-induced G2 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, T288. We find that decreased AurA-TPX2 complex formation in response to irradiation results from reduced cellular levels of TPX2, an effect that is both contributed by increased APC/CDH1-dependent protein degradation and decreased translation of TPX2 mRNA.
History
Publication status
- Published
Journal
Cell CycleISSN
1538-4101External DOI
Issue
22Volume
9Page range
4592-4599Pages
8.0Department affiliated with
- Biochemistry Publications
Full text available
- No
Peer reviewed?
- Yes
Legacy Posted Date
2012-02-06Usage metrics
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