Identification of interleukin-1 receptor-associated kinase 1 as a critical component that induces post-transcriptional activation of IκB-ζ

Authors

  • Tomoyuki Ohba,

    1.  Laboratory of Cell Recognition and Response, Department of Developmental Biology and Neurosciences, Graduate School of Life Sciences, Tohoku University, Sendai, Japan
    2.  Department of Biology, Faculty of Science, Tohoku University, Sendai, Japan
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  • Yujiro Ariga,

    1.  Laboratory of Cell Recognition and Response, Department of Developmental Biology and Neurosciences, Graduate School of Life Sciences, Tohoku University, Sendai, Japan
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  • Takashi Maruyama,

    1.  Laboratory of Cell Recognition and Response, Department of Developmental Biology and Neurosciences, Graduate School of Life Sciences, Tohoku University, Sendai, Japan
    2.  Department of Biology, Faculty of Science, Tohoku University, Sendai, Japan
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  • Nha K. Truong,

    1.  Department of Biology, Faculty of Science, Tohoku University, Sendai, Japan
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  • Jun-ichiro Inoue,

    1.  Division of Cellular and Molecular Biology, Department of Cancer Biology, Institute of Medical Science, University of Tokyo, Japan
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  • Tatsushi Muta

    1.  Laboratory of Cell Recognition and Response, Department of Developmental Biology and Neurosciences, Graduate School of Life Sciences, Tohoku University, Sendai, Japan
    2.  Department of Biology, Faculty of Science, Tohoku University, Sendai, Japan
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T. Muta, 6-3 Aoba, Aramaki, Aoba-ku, Sendai 980-8578, Japan
Fax: +81 22 795 6709
Tel: +81 22 795 6709
E-mail: tmuta@biology.tohoku.ac.jp

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.

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