کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
2160638 1090890 2008 8 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
The radioprotector Bowman–Birk proteinase inhibitor stimulates DNA repair via epidermal growth factor receptor phosphorylation and nuclear transport
موضوعات مرتبط
علوم زیستی و بیوفناوری بیوشیمی، ژنتیک و زیست شناسی مولکولی تحقیقات سرطان
پیش نمایش صفحه اول مقاله
The radioprotector Bowman–Birk proteinase inhibitor stimulates DNA repair via epidermal growth factor receptor phosphorylation and nuclear transport
چکیده انگلیسی

Background and purposeThe purpose of the study was to elucidate the underlying molecular mechanism of the radioprotector, Bowman–Birk proteinase inhibitor (BBI), and its interaction with EGFR nuclear transport.Materials and methodsMolecular effects of BBI at the level of EGFR responses were investigated in vitro with wt. TP53 bronchial carcinoma cell line A549 and the transformed fibroblast cell line HH4dd characterized by a mt. TP53. EGFR and associated protein expression were quantified by Western blotting and confocal microscopy in the cytoplasmic and nuclear cell fraction. Residual DNA double strand breaks were quantified by means of a γH2AX focus assay.ResultsBoth irradiation and BBI-treatment stimulated EGFR internalization into the cytoplasm. This process involved src kinase activation, EGFR phosphorylation at Y845, and caveolin 1 phosphorylation at Y14. EGFR internalization correlated with nuclear EGFR transport and was associated with phosphorylation of EGFR at T654. Nuclear EGFR was linked with DNA-PK complex formation and activation. Furthermore, nuclear EGFR was found in complex with TP53, phosphorylated at S15, and with MDC1, following irradiation and BBI treatment. It is noteworthy that MDC1 was strongly decreased in the nuclear EGFR complex in cells with mt. TP53 and failed to be increased by either BBI treatment or irradiation. Interestingly, in cells with mt. TP53 the BBI mediated stimulation of double strand break repair was hampered significantly.ConclusionThese data indicate that BBI stimulates complex formation between EGFR, TP53 and MDC1 protein in wt. TP53 cells only. Since MDC1 is essential for recruitment of DNA repair foci, this observation may explain how BBI selectively stimulated repair of DNA double strand breaks in wt. TP53 cells.

ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Radiotherapy and Oncology - Volume 86, Issue 3, March 2008, Pages 375–382
نویسندگان
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