ATM-dependent phosphorylation of ATF2 is required for the DNA damage response
ATM-dependent phosphorylation of ATF2 is required for the DNA damage response
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DOI：
10.1016/j.molcel.2005.04.015
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发表时间：
2005-05-27
期刊：
影响因子：
16
通讯作者：
Ronai, Z
中科院分区：
文献类型：
--
作者：
Bhoumik, A;Takahashi, S;Ronai, Z
激活转录因子2（ATF 2）受JNK/p38调节以响应应激。在这里，我们证明了蛋白激酶ATM磷酸化ATF 2丝氨酸490和498电离辐射（IR）后。ATF 2 49018的磷酸化抗体揭示了ATM对ATF 2的剂量和时间依赖性磷酸化，导致其与γ-H2 AX和MRN组分快速共定位到IR诱导的病灶（IRIF）中。抑制ATF 2表达可减少Mre 11向IRIF的募集，废除S期检查点，减少ATM、Chk 1和Chk 2的激活，并损害放射抗性。ATF 2既不需要JNK/p38也不需要其DNA结合结构域来募集到IRIF和S期检查点。我们的研究结果确定了ATF 2在DNA损伤反应中的作用，该作用与其转录活性无关。
Activating transcription factor 2 (ATF2) is regulated by JNK/p38 in response to stress. Here, we demonstrate that the protein kinase ATM phosphorylates ATF2 on serines 490 and 498 following ionizing radiation (IR). Phosphoantibodies to ATF2 49018 reveal dose-and time-dependent phosphorylation of ATF2 by ATM that results in its rapid colocalization with gamma-H2AX and MRN components into IR-Induced foci (IRIF). Inhibition of ATF2 expression decreased recruitment of Mre11 to IRIF, abrogated S phase checkpoint, reduced activation of ATM, Chk1, and Chk2, and impaired radioresistance. ATF2 requires neither JNK/p38 nor its DNA binding domain for recruitment to IRIF and the S phase checkpoint. Our findings identify a role for ATF2 in the DNA damage response that is uncoupled from its transcriptional activity.