FLN29 deficiency reveals its negative regulatory role in the toll-like receptor (TLR) and retinoic acid-inducible gene I (RIG-I)-like helicase signaling pathway

Takahito Sanada, Giichi Takaesu, Ryuichi Mashima, Ryoko Yoshida, Takashi Kobayashi, Akihiko Yoshimura

Research output: Contribution to journalArticle

34 Citations (Scopus)

Abstract

FLN29 was identified as an interferon (IFN)-inducible gene, and it has been shown to suppress Toll-like receptor 4-mediated NF-κB activation by binding to TRAF6. To elucidate the physiological roles of FLN29, we generated FLN29-deficient mice. FLN29 deficiency resulted in hyper-response to LPS both in vivo and in vitro, demonstrating the negative regulatory role of FLN29 in TLR4 signaling. Furthermore, we found that FLN29-/- mice exhibited increased susceptibility to poly(I:C)-induced septic shock compared with WT mice. FLN29-/- fibroblasts were highly resistant to vesicular stomatitis virus infection, and these cells produced more IFN-β than WT cells did in response to not only intracellular poly(I:C) but also overexpression of IPS-1. Forced expression of FLN29 inhibited the IPS-1-dependent activation of both NF-κB and IRF3. We also found that FLN29 could interact with TRIF, IPS-1, TRAF3, and TRAF6. Together, these results suggest that FLN29, in addition to playing a negative regulatory role in the TLR4 signaling pathway, negatively regulates the RIG-I-like helicase signaling pathway at the level of IPS-1/TRAF6 and IPS-1/TRAF3 complexes.

Original languageEnglish
Pages (from-to)33858-33864
Number of pages7
JournalJournal of Biological Chemistry
Volume283
Issue number49
DOIs
Publication statusPublished - 2008 Dec 5

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TNF Receptor-Associated Factor 6
Toll-Like Receptors
TNF Receptor-Associated Factor 3
Tretinoin
Poly I-C
Genes
Interferons
Chemical activation
Vesicular Stomatitis
Toll-Like Receptor 4
Virus Diseases
Fibroblasts
Septic Shock
Viruses
polyriboinosinic-polyribocytidylic acid

ASJC Scopus subject areas

  • Biochemistry
  • Cell Biology
  • Molecular Biology

Cite this

FLN29 deficiency reveals its negative regulatory role in the toll-like receptor (TLR) and retinoic acid-inducible gene I (RIG-I)-like helicase signaling pathway. / Sanada, Takahito; Takaesu, Giichi; Mashima, Ryuichi; Yoshida, Ryoko; Kobayashi, Takashi; Yoshimura, Akihiko.

In: Journal of Biological Chemistry, Vol. 283, No. 49, 05.12.2008, p. 33858-33864.

Research output: Contribution to journalArticle

Sanada, Takahito ; Takaesu, Giichi ; Mashima, Ryuichi ; Yoshida, Ryoko ; Kobayashi, Takashi ; Yoshimura, Akihiko. / FLN29 deficiency reveals its negative regulatory role in the toll-like receptor (TLR) and retinoic acid-inducible gene I (RIG-I)-like helicase signaling pathway. In: Journal of Biological Chemistry. 2008 ; Vol. 283, No. 49. pp. 33858-33864.
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