کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
10815793 | 1058503 | 2010 | 11 صفحه PDF | دانلود رایگان |
عنوان انگلیسی مقاله ISI
IKKα negatively regulates IRF-5 function in a MyD88-TRAF6 pathway
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موضوعات مرتبط
علوم زیستی و بیوفناوری
بیوشیمی، ژنتیک و زیست شناسی مولکولی
زیست شیمی
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چکیده انگلیسی
Transcription factors of IRF family, IRF-3, IRF-5 and IRF-7 play a critical role in the innate antiviral response. In infected cells, IRF-3 and IRF-7 are activated by TBK-1 and IKKε mediated phosphorylation, while the kinase, phosphorylating IRF-5 in the MyD88 signalling pathway has not yet been identified. We now show that IKKα phosphorylates IRF-5 and induces formation of IRF-5 dimers, which have been indicative of IRF-5 activation. However, IKKα induced IRF-5 phosphorylation exerts inhibitory effect on the transcriptional activation of type 1 interferon and promoters of the inflammatory cytokines. Addressing the molecular mechanism of IKKα mediated inhibition of IRF-5 activity, we show that phosphorylation of IRF-5 by IKKα inhibits K63 ubiquitination that is essential for IRF-5 activity. Furthermore, we have identified interaction of IRF-5 with alkaline phosphatase, which causes its de-phosphorylation. The observation that MyD88 activated IRF-5 induces expression of alkaline phosphatase suggests that IRF-5 is under autoregulating loop. Thus these completely new observations identify IKKα kinase and alkaline phosphatase as negative regulators of IRF-5 activity in MyD88 pathway and implicate their role in the control of the inflammatory response by attenuation of IRF-5 activity.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Cellular Signalling - Volume 22, Issue 1, January 2010, Pages 117-127
Journal: Cellular Signalling - Volume 22, Issue 1, January 2010, Pages 117-127
نویسندگان
Mumtaz Yaseen Balkhi, Katherine A. Fitzgerald, Paula M. Pitha,