ATM-dependent phosphorylation of heterogeneous nuclear ribonucleoprotein K promotes p53 transcriptional activation in response to DNA damage.

ATM-dependent phosphorylation of heterogeneous nuclear ribonucleoprotein K promotes p53 transcriptional activation in response to DNA damage.
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DOI:
10.4161/cc.23592
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发表时间:
2013-02-15
期刊:
Cell cycle (Georgetown, Tex.)
影响因子:
--
通讯作者:
Jackson SP
Jackson SP
中科院分区:
其他
文献类型:
--
作者:
Moumen A;Magill C;Dry KL;Jackson SP

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先前的工作已经证实,异质核核糖核蛋白 K (hnRNP K) 在响应 DNA 损伤时以 ATM 依赖性方式稳定,并充当 p53 介导的转录的辅助因子。在这里,我们发现,为了响应电离辐射引起的 DNA 损伤,hnRNP K 以 ATM 依赖性方式磷酸化。此外,我们的数据表明,ATM 依赖性 hnRNP K 磷酸化是其稳定性及其作为 p53 转录辅助因子响应 DNA 损伤的功能所必需的。因此,这些发现将 hnRNP K 确立为 ATM 靶标,并有助于确定 ATM 如何协调 p53 依赖性转录反应以应对基因毒性应激。
Previous work has established that heterogeneous nuclear ribonucleoprotein K (hnRNP K) is stabilized in an ATM-dependent manner in response to DNA damage and acts as a cofactor for p53-mediated transcription. Here, we show that in response to DNA damage caused by ionizing radiation, hnRNP K is phosphorylated in an ATM-dependent manner. Furthermore, our data indicate that ATM-dependent hnRNP K phosphorylation is required for its stabilization and its function as a p53 transcriptional cofactor in response to DNA damage. These findings thereby establish hnRNP K as an ATM target and help define how ATM orchestrates p53-dependent transcriptional responses in response to genotoxic stress.
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