DNA Damage Response Group, Basic Medical Science Department, St. George's University of London, London, UK.
Cell Cycle. 2013 Feb 15;12(4):698-704. doi: 10.4161/cc.23592. Epub 2013 Jan 23.
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.
先前的研究已经证实,异质核核糖核蛋白 K(hnRNP K)在 DNA 损伤的情况下以 ATM 依赖性的方式稳定,并作为 p53 介导的转录的辅助因子发挥作用。在这里,我们表明,在对电离辐射引起的 DNA 损伤的反应中,hnRNP K 以 ATM 依赖性的方式发生磷酸化。此外,我们的数据表明,ATM 依赖性 hnRNP K 磷酸化是其稳定和作为 p53 转录辅助因子在 DNA 损伤反应中的功能所必需的。这些发现因此确立了 hnRNP K 是 ATM 的靶标,并有助于确定 ATM 如何在基因毒性应激下协调 p53 依赖性转录反应。