title: Identification of interleukin-1 receptor-associated kinase 1 as a critical component that induces post-transcriptional activation of IκB-ζ.
abstract: IκB-ζ, an essential inflammatory regulator, is specifically induced by Toll-like receptor ligands or interleukin (IL)-1β by post-transcriptional activation mediated via a 165-nucleotide element in IκB-ζ mRNA. Here, we analyzed the Toll-like receptor-IL-1 receptor signaling components involved in the post-transcriptional regulation of IκB-ζ with mutated estrogen receptor [ER(T2)] fusion proteins. Upon 4-hydroxytamoxifen treatment, the ER(T2) fusion proteins with IL-1 receptor-associated kinase (IRAK)1 and IRAK4 elicited specific activation of a reporter gene for the post-transcriptional regulation of IκB-ζ. The tumor necrosis factor receptor-associated factor (TRAF)6-ER(T2) protein activated nuclear factor-κB, but not post-transcriptional regulation, indicating that activation of IRAK1/4, but not of TRAF6, is sufficient to activate the 165-nucleotide element-mediated post-transcriptional mechanism. Interestingly, the post-transcriptional mechanism was not activated in TRAF6-deficient cells, indicating an essential role for TRAF6. Thus, the signaling pathway leading to nuclear factor-κB activation and the post-transcriptional activation bifurcates at IRAK1, suggesting a new pathway activated by IRAK1.
authors: Laboratory of Cell Recognition and Response, Department of Developmental Biology and Neurosciences, Graduate School of Life Sciences, Tohoku University, Sendai, Japan.
authors: Tomoyuki
authors: T
authors: Ohba
authors: Yujiro
authors: Y
authors: Ariga
authors: Takashi
authors: T
authors: Maruyama
authors: Nha K
authors: NK
authors: Truong
authors: Jun-ichiro
authors: J
authors: Inoue
authors: Tatsushi
authors: T
authors: Muta
mesh_terms: D048868:Adaptor Proteins, Signal Transducing; D000818:Animals; D002478:Cells, Cultured; D004622:Embryo, Mammalian / Q000166:cytology; D020847:Estrogen Receptor Modulators / Q000494:pharmacology; D047629:Estrogen Receptor beta / Q000819:agonists / Q000235:genetics / Q000378:metabolism; D020868:Gene Silencing; D017930:Genes, Reporter / Q000187:drug effects; D057809:HEK293 Cells; D006801:Humans; D020672:I-kappa B Proteins; D053592:Interleukin-1 Receptor-Associated Kinases / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D050505:Mutant Proteins / Q000037:antagonists & inhibitors / Q000378:metabolism; D016328:NF-kappa B / Q000235:genetics / Q000378:metabolism; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism*; D012323:RNA Processing, Post-Transcriptional; D012333:RNA, Messenger / Q000378:metabolism*; D011993:Recombinant Fusion Proteins / Q000819:agonists / Q000037:antagonists & inhibitors / Q000378:metabolism; D011994:Recombinant Proteins / Q000378:metabolism; D048029:TNF Receptor-Associated Factor 6 / Q000235:genetics / Q000378:metabolism
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D020847:Estrogen Receptor Modulators; D047629:Estrogen Receptor beta; D020672:I-kappa B Proteins; D050505:Mutant Proteins; D016328:NF-kappa B; C417234:NFKBIZ protein, human; D009687:Nuclear Proteins; D012333:RNA, Messenger; D011993:Recombinant Fusion Proteins; D011994:Recombinant Proteins; D048029:TNF Receptor-Associated Factor 6; C507768:IRAK1 protein, human; C507773:IRAK4 protein, human; D053592:Interleukin-1 Receptor-Associated Kinases