Mitotic DNA damage targets the Aurora A/TPX2 complex

被引：6

作者：

Bhatia, Payal ^{[1
]}

Menigatti, Mirco ^{[1
]}

Brocard, Michele ^{[2
]}

Morley, Simon ^{[2
]}

Ferrari, Stefano ^{[1
]}

机构：

[1] Univ Zurich, Inst Mol Canc Res, Zurich, Switzerland

[2] Univ Sussex, Sch Life Sci, Dept Biochem, Falmer, England

来源：

CELL CYCLE | 2010年 / 9卷 / 22期

基金：

英国生物技术与生命科学研究理事会;

关键词：

Aurora A; DNA damage; mitosis; TPX2; translation; B1; MESSENGER-RNA; CHROMOSOME SEGREGATION; TRANSLATIONAL CONTROL; STRUCTURAL BASIS; CELL-DIVISION; KINASE; ACTIVATION; CHECKPOINT; MITOSIS; PHOSPHORYLATION;

D O I：

10.4161/cc.9.22.13665

中图分类号：

Q2 [细胞生物学];

学科分类号：

071009 ; 090102 ;

摘要：

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.

引用

页码：4592 / 4599

页数：8

共 48 条

[1] The Cdc14B-Cdh1-Plk1 axis controls the G2 DNA-damage-response checkpoint [J].