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FLN29, a novel interferon- and LPS-inducible gene acting as a negative regulator of toll-like receptor signaling

Authors :
Takashi Kobayashi
Hiromi Takaki
Kazuko Saeki
Daisuke Aki
Yasumasa Minoda
Hiroyuki Aburatani
Ryuichi Mashima
Yuji Yamanashi
Takahito Sanada
Akihiko Yoshimura
Source :
The Journal of biological chemistry. 280(50)
Publication Year :
2005

Abstract

Lipopolysaccharide (LPS) activates macrophages through toll-like receptor (TLR) 4. Although the mechanism of the TLR signaling pathway has been well documented, the mechanism of the negative regulation in response to LPS, particularly LPS tolerance, is still poorly understood. In this study we identified and characterized a novel interferon- and LPS-inducible gene, FLN29, which contains a TRAF6-related zinc finger motif and TRAF family member-associated NF-kappaB activator-related sequences. The induction of FLN29 was dependent on STAT1. The forced expression of FLN29 in macrophage-like RAW cells resulted in the suppression of TLR-mediated NF-kappaB and mitogen-activated protein kinase activation, while a reduced expression of FLN29 by small interfering RNA partly cancelled the down-regulation of LPS signaling. Furthermore, we demonstrated that NF-kappaB activation induced by TRAF6 and TAB2 was impaired by co-expression of FLN29, suggesting FLN29 may regulate the downstream of TRAF6. Taken together, FLN29 is a new negative feedback regulator of TLR signaling.

Details

ISSN :
00219258
Volume :
280
Issue :
50
Database :
OpenAIRE
Journal :
The Journal of biological chemistry
Accession number :
edsair.doi.dedup.....c6dd6b41b8d06131a02e7b5cfe650a2f