Radiation-induced epidermal growth factor receptor nuclear import is linked to activation of DNA-dependent protein kinase
Radiation-induced epidermal growth factor receptor nuclear import is linked to activation of DNA-dependent protein kinase
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DOI：
10.1074/jbc.m506591200
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发表时间：
2005-09-02
影响因子：
4.8
通讯作者：
Rodemann, HP
中科院分区：
文献类型：
--
作者：
Dittmann, K;Mayer, C;Rodemann, HP
电离辐射，而不是表皮生长因子（EGF）的刺激，触发EGF受体（EGFR）以可能与核细胞蛋白相关的方式进入细胞核。在H2O2、高温或顺铂治疗后，也观察到核EGFR的增加。在这个过程中，蛋白Ku70/80和蛋白磷酸酶1被转运到细胞核中。结果，DNA依赖性激酶（DNA- pk）的核激酶活性增加，含有DNA- pk的DNA末端结合蛋白复合物的形成增加，这对DNA链断裂的修复至关重要。通过抗EGFR单克隆抗体C225阻断EGFR输入，可消除EGFR输入细胞核和辐射诱导的DNA- pk激活，抑制DNA修复，增加处理细胞的放射敏感性。我们的数据暗示了EGFR在DNA修复过程中的一种新功能。
Ionizing radiation, but not stimulation with epidermal growth factor (EGF), triggers EGF receptor ( EGFR) import into the nucleus in a probably karyopherin alpha-linked manner. An increase in nuclear EGFR is also observed after treatment with H2O2, heat, or cisplatin. During this process, the proteins Ku70/80 and the protein phosphatase 1 are transported into the nucleus. As a consequence, an increase in the nuclear kinase activity of DNA-dependent kinase (DNA-PK) and increased formation of the DNA end-binding protein complexes containing DNA-PK, essential for repair of DNA-strand breaks, occurred. Blockade of EGFR import by the anti-EGFR monoclonal antibody C225 abolished EGFR import into the nucleus and radiation-induced activation of DNA-PK, inhibited DNA repair, and increased radiosensitivity of treated cells. Our data implicate a novel function of the EGFR during DNA repair processes.