TY - JOUR
T1 - Radiation-induced epidermal growth factor receptor nuclear import is linked to activation of DNA-dependent protein kinase
AU - Dittmann, Klaus
AU - Mayer, Claus
AU - Fehrenbacher, Birgit
AU - Schaller, Martin
AU - Raju, Uma
AU - Milas, Luka
AU - Chen, David J.
AU - Kehlbach, Rainer
AU - Rodemann, H. Peter
PY - 2005/9/2
Y1 - 2005/9/2
N2 - 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.
AB - 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.
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U2 - 10.1074/jbc.M506591200
DO - 10.1074/jbc.M506591200
M3 - Article
C2 - 16000298
AN - SCOPUS:24744449739
SN - 0021-9258
VL - 280
SP - 31182
EP - 31189
JO - Journal of Biological Chemistry
JF - Journal of Biological Chemistry
IS - 35
ER -