Permanent URL to this publication: http://dx.doi.org/10.5167/uzh-46440
Bhatia, P; Menigatti, M; Brocard, M; Morley, S J; Ferrari, S (2010). Mitotic DNA damage targets the Aurora A/TPX2 complex. Cell Cycle, 9(22):4592-4599.
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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.
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|Item Type:||Journal Article, refereed, original work|
|Communities & Collections:||04 Faculty of Medicine > Institute of Molecular Cancer Research
07 Faculty of Science > Institute of Molecular Cancer Research
|DDC:||570 Life sciences; biology|
|Deposited On:||22 Feb 2011 19:40|
|Last Modified:||03 Dec 2013 14:10|
|Free access at:||Publisher DOI. An embargo period may apply.|
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