Mitotic DNA damage targets the Aurora A/TPX2 complex

Bhatia, Payal, Menigatti, Mirco, Brocard, Michele, Morley, Simon J and Ferrari, Stefano (2010) Mitotic DNA damage targets the Aurora A/TPX2 complex. Cell Cycle, 9 (22). pp. 4592-4599. ISSN 1538-4101

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We 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.

Item Type: Article
Schools and Departments: School of Life Sciences > Biochemistry
Depositing User: Simon Morley
Date Deposited: 06 Feb 2012 20:07
Last Modified: 30 Nov 2012 17:05
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