Radiation-induced epidermal growth factor receptor nuclear import is linked to activation of DNA-dependent protein kinase

Klaus Dittmann, Claus Mayer, Birgit Fehrenbacher, Martin Schaller, Uma Raju, Luka Milas, David J. Chen, Rainer Kehlbach, H. Peter Rodemann

Research output: Contribution to journalArticlepeer-review

428 Scopus citations

Abstract

Ionizing radiation, but not stimulation with epidermal growth factor (EGF), triggers EGF receptor (EGFR) import into the nucleus in a probably karyopherin á-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-EGFK monoclonal antibody C225 abolished EGFR import into the nucleus and radiation-induced activation of DNA-PK, inhibited DNA repair, and increased radio-sensitivity of treated cells. Our data implicate a novel function of the EGFR during DNA repair processes.

Original languageEnglish (US)
Pages (from-to)31182-31189
Number of pages8
JournalJournal of Biological Chemistry
Volume280
Issue number35
DOIs
StatePublished - Sep 2 2005

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

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