ATMINistrating ATM signalling Regulation of ATM by ATMIN
ATMINistrating ATM signalling Regulation of ATM by ATMIN
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DOI：
10.4161/cc.7.22.7044
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发表时间：
2008-11-15
期刊：
影响因子：
4.3
通讯作者：
Behrens, Axel
中科院分区：
文献类型：
--
作者：
Kanu, Nnennaya;Behrens, Axel
检查点激酶ATM（共济失调毛细血管扩张突变）转导基因组应激信号，以停止细胞周期进程并促进DNA修复以应对DNA损伤。我们最近发现了ATM的一个重要辅因子，ATMIN（ATM互作用子）。一些观察表明，ATMIN在ATM信号中起着关键作用。ATMIN和ATM蛋白质的稳定性是相互依赖的，这表明一个密切的物理和功能的相互作用。ATMIN使用短羧基末端基序结合ATM，其方式类似于另一种ATM辅因子Nijmegen断裂综合征蛋白1（NBS1）与ATM的结合方式。ATMIN和NBS1在ATM信号转导中具有互补功能。ATMIN是由氯喹和低渗应激的ATM信号传导所需的，但不是在电离辐射（IR）诱导双链断裂后，而NBS1是由IR的ATM信号传导所需的。这表明NBS1和ATMIN以信号依赖的方式竞争ATM结合。这些研究结果的ATM信号通路的一些影响进行了讨论。
The checkpoint kinase ATM (ataxia telangiectasia mutated) transduces genomic stress signals to halt cell cycle progression and promote DNA repair in response to DNA damage. We have recently identified an essential cofactor for ATM, ATMIN (for ATM INteractor). Several observations suggested that ATMIN plays a key role in ATM signalling. ATMIN and ATM protein stability were mutually dependent, which indicated an intimate physical and functional interaction. ATMIN bound ATM using a short carboxy-terminal motif, in a manner analogous to how another ATM cofactor, Nijmegen Breakage Syndrome protein 1 (NBS1), associates with ATM. ATMIN and NBS1 had complementary functions in ATM signalling. ATMIN was required for ATM signalling by chloroquine and hypotonic stress, but not after induction of double-stand breaks by ionizing radiation (IR), whereas NBS1 is required for ATM signalling by IR. This suggested competition of NBS1 and ATMIN for ATM binding in a signal-dependent fashion. Some implications of these findings for the ATM signalling pathway are discussed.