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- Title
Nuclear EGFR shuttling induced by ionizing radiation is regulated by phosphorylation at residue Thr654
- Authors
Dittmann, Klaus; Mayer, Claus; Fehrenbacher, Birgit; Schaller, Martin; Kehlbach, Rainer; Rodemann, H. Peter
- Abstract
Abstract: Nuclear localisation of EGFR is associated with treatment resistance of tumor cells. The aim of this study was to identify molecular targets to block nuclear shuttling of EGFR. Mutation of Thr654, located within the putative EGFR NLS demonstrated that phosphorylation of this residue is essential for nuclear EGFR shuttling following irradiation. Deletion of Thr654 blocked nuclear transport of EGFR, whereas mutation to Glu increased shuttling. Treatment with a peptide, corresponding to the phosphorylated NLS, abolished nuclear EGFR transport and reduced radiation-induced activation of DNA-PK, essential for DNA-repair. In accordance with that, lack of nuclear EGFR increased residual DNA damage in tumor cells and reduced cellular survival following irradiation. Blockage of nuclear EGFR shuttling may be a new strategy to fight treatment resistance. Structured summary: MINT-7987956: Karyopherin alpha (uniprotkb:P52294) physically interacts (MI:0915) with EGFR (uniprotkb:P00533) by anti bait coimmunoprecipitation (MI:0006)
- Subjects
EPIDERMAL growth factor; CELL receptors; IONIZING radiation; PHOSPHORYLATION; CANCER cells; CANCER treatment; DNA repair
- Publication
FEBS Letters, 2010, Vol 584, Issue 18, p3878
- ISSN
0014-5793
- Publication type
Article
- DOI
10.1016/j.febslet.2010.08.005