The IκB kinase complex regulates the stability of cytokine-encoding mRNA induced by TLR-IL-1R by controlling degradation of regnase-1

Hidenori Iwasaki, Osamu Takeuchi, Shunsuke Teraguchi, Kazufumi Matsushita, Takuya Uehata, Kanako Kuniyoshi, Takashi Satoh, Tatsuya Saitoh, Mutsuyoshi Matsushita, Daron M. Standley, Shizuo Akira

Research output: Contribution to journalArticlepeer-review

152 Citations (Scopus)

Abstract

Toll-like receptor (TLR) signaling activates the inhibitor of transcription factor NF-κB (IκB) kinase (IKK) complex, which governs NF-κB-mediated transcription during inflammation. The RNase regnase-1 serves a critical role in preventing autoimmunity by controlling the stability of mRNAs that encode cytokines. Here we show that the IKK complex controlled the stability of mRNA for interleukin 6 (IL-6) by phosphorylating regnase-1 in response to stimulation via the IL-1 receptor (IL-1R) or TLR. Phosphorylated regnase-1 underwent ubiquitination and degradation. Regnase-1 was reexpressed in IL-1R-or TLR-activated cells after a period of lower expression. Regnase-1 mRNA was negatively regulated by regnase-1 itself via a stem-loop region present in the regnase-1 3ĝ€2 untranslated region. Our data demonstrate that the IKK complex phosphorylates not only IκBÎ ±, thereby activating transcription, but also regnase-1, thereby releasing a 'brake' on IL-6 mRNA expression.

Original languageEnglish
Pages (from-to)1167-1175
Number of pages9
JournalNature Immunology
Volume12
Issue number12
DOIs
Publication statusPublished - 2011 Dec

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

Fingerprint Dive into the research topics of 'The IκB kinase complex regulates the stability of cytokine-encoding mRNA induced by TLR-IL-1R by controlling degradation of regnase-1'. Together they form a unique fingerprint.

Cite this