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

Tomoyuki Ohba, Yujiro Ariga, Takashi Maruyama, Nha K. Truong, Jun Ichiro Inoue, Tatsushi Muta

Research output: Contribution to journalArticlepeer-review

12 Citations (Scopus)

Abstract

Iκ-B¶-I¶, 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 Iκ-B¶-I;¶ mRNA. Here, we analyzed the Toll-like receptor-IL-1 receptor signaling components involved in the post-transcriptional regulation of Iκ-B¶-I¶ 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 Iκ-B¶-I¶. 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. Iκ-B¶-I¶, an essential inflammatory regulator, is specifically induced by Toll-like receptor ligands or interleukin-1β by post-transcriptional activation via a 165-nucleotide element in Iκ-B¶-I¶ mRNA. Here, we found that while either IRAK1/4 or TRAF6 induces NF-κB activation, activation of IRAK1/4, but not that of TRAF6, are sufficient to elicit the post-transcriptional activation of Iκ-B¶-I¶, suggesting a new pathway activated by IRAK1.

Original languageEnglish
Pages (from-to)211-222
Number of pages12
JournalFEBS Journal
Volume279
Issue number2
DOIs
Publication statusPublished - 2012 Jan

Keywords

  • Iκ-B¶-I¶
  • Toll-like receptor
  • interleukin-1 (IL-1)
  • interleukin-1 receptor-associated kinase (IRAK1)
  • post-transcriptional regulation

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

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