Journal of Biological Chemistry
Volume 280, Issue 35, 2 September 2005, Pages 31182-31189
Journal home page for Journal of Biological Chemistry

DNA: Replication, Repair, and Recombination
Radiation-induced Epidermal Growth Factor Receptor Nuclear Import Is Linked to Activation of DNA-dependent Protein Kinase*

https://doi.org/10.1074/jbc.M506591200Get rights and content
Under a Creative Commons license
open access

Ionizing radiation, but not stimulation with epidermal growth factor (EGF), triggers EGF receptor (EGFR) import into the nucleus in a probably karyopherin α-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.

Cited by (0)

*

The work was supported by the Fortüne Program Nr. 1022 and 1399-0-0 and BMBF-IZKF-project B6 (01KS9602), Deutsche Krebshilfe Grant 106401, National Institutes of Health Grant CA06294, and NCI, National Institutes of Health Cancer Center Core Grant CA16672. The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked “advertisement” in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.