کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
1963957 1058518 2008 11 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
Ionizing radiation can induce GSK-3β phosphorylation and NF-κB transcriptional transactivation in ATM-deficient fibroblasts
موضوعات مرتبط
علوم زیستی و بیوفناوری بیوشیمی، ژنتیک و زیست شناسی مولکولی زیست شیمی
پیش نمایش صفحه اول مقاله
Ionizing radiation can induce GSK-3β phosphorylation and NF-κB transcriptional transactivation in ATM-deficient fibroblasts
چکیده انگلیسی

DNA damage by ionizing radiation (IR) can induce activations of both NF-κB and p53 through the upstream kinase ataxia telangiectasia mutated (ATM). NF-κB activation could also be signaled through two distinct or overlapped pathways; IκB kinases (IKKs)-IκBα and Akt–glycogen synthase kinase-3 (GSK-3). In the present study, however, we show that activation of Akt1 and the subsequent phosphorylation and inactivation of GSK-3β by IR could also occur in ATM-deficient AT5BIVA cells as well as in normal MRC5CV1 fibroblasts. Similarly, lithium chloride (LiCl) was found to increase the phosphorylation of GSK-3β independently of ATM. Transfection with either wild-type or kinase dead mutant GSK-3β to the cells further indicated that phosphorylations of Akt1 and GSK-3β were closely associated with the transcriptional transactivation of NF-κB in response to ionizing radiation. On the other hand, LiCl, having no effect on caspase-3 activation, significantly increased p53 phosphorylation and apoptotic death of the normal MRC5CV1 cells while IR, activating both caspase-3 and p53, profoundly affected AT5BIVA cell death. Hence, our data suggest that although ATM-mediated IKK–IκBα pathway might be a typical pathway for IR-induced NF-κB activation, GSK-3β phosphorylation could also partially contribute to the transcriptional transactivation of NF-κB in an ATM-independent manner and that GSK-3β phosphorylation could induce ATM-mediated cell apoptosis through the activation of p53.

ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Cellular Signalling - Volume 20, Issue 4, April 2008, Pages 602–612
نویسندگان
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