کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
1964066 1058524 2008 7 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
GβL regulates TNFα-induced NF-кB signaling by directly inhibiting the activation of IкB kinase
موضوعات مرتبط
علوم زیستی و بیوفناوری بیوشیمی، ژنتیک و زیست شناسی مولکولی زیست شیمی
پیش نمایش صفحه اول مقاله
GβL regulates TNFα-induced NF-кB signaling by directly inhibiting the activation of IкB kinase
چکیده انگلیسی

The transcriptional activation of NF-кB, a critical player in both physiological and pathological cellular responses to diverse cytokines, is dependent on IKK activation. Although molecular mechanisms underlying IKK activation have been well elucidated, the processes that negatively regulate IKK activity are still largely unknown. Using yeast two-hybrid screening, we have identified GβL as an interacting partner of IKKβ. In this study, we demonstrate that GβL interacts with IKKα and IKKβ in vitro and in vivo. The C-terminal WD domains of GβL are required for the interaction with both the kinase domain and leucine zipper domain of IKKβ. Overexpression of GβL inhibits TNFα-induced activation of NF-кB signaling, while down-regulation of GβL expression by small interfering RNA enhances NF-кB activity. GβL constitutively interacts with IKKβ, and this interaction is enhanced by TNFα treatment. GβL also inhibits TNFα-induced phosphorylation of IKKs. Taken together, these data suggest that GβL is involved in the negative regulation of TNFα-stimulated NF-кB signaling through a direct interaction with IKK.

ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Cellular Signalling - Volume 20, Issue 11, November 2008, Pages 2127–2133
نویسندگان
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