DOI: 10.4049/jimmunol.171.8.4304. Toll/IL-1 Receptor Domain-Containing Adaptor Inducing IFN-β (TRIF) Associates with TNF Receptor-Associated Factor 6 and TANK-Binding Kinase 1, and Activates Two Distinct Transcription Factors, NF-κB and IFN-Regulatory Factor-3, in the Toll-Like Receptor Signaling

Toll/IL-1 Receptor Domain-Containing Adaptor Inducing IFN-β (TRIF) Associates with TNF Receptor-Associated Factor 6 and TANK-Binding Kinase 1, and Activates Two Distinct Transcription Factors, NF-κB and IFN-Regulatory Factor-3, in the Toll-Like Receptor Signaling

10.4049/jimmunol.171.8.4304

Crossref journal-article

Oxford University Press (OUP)

The Journal of Immunology (286)

Abstract

Abstract We previously reported a new Toll/IL-1R (TIR)-containing molecule, named TIR domain-containing adaptor inducing IFN-β (TRIF). Although initial study indicated that TRIF possesses the ability to activate not only the NF-κB-dependent but also the IFN-β promoters, the molecular mechanisms of TRIF-induced signaling are poorly understood. In this study, we investigated the signaling cascades through TRIF. TNF receptor-associated factor (TRAF)6 interacted with TRIF through the TRAF domain of TRAF6 and TRAF6-binding motifs found in the N-terminal portion of TRIF. Disruption of TRAF6-binding motifs of TRIF disabled it from associating with TRAF6, and resulted in a reduction in the TRIF-induced activation of the NF-κB-dependent but not IFN-β promoter. TANK-binding kinase (TBK)-1, which was recently reported to be a kinase of IFN regulatory factor-3, which is an essential transcription factor for IFN-β expression, also associated with the N-terminal region of TRIF. Moreover, the association between TRIF and TBK1 appeared to require the kinase activity of TBK1, as well as phosphorylation of TRIF. Because TRAF6 and TBK1 bind close the region of TRIF, it seems that TRAF6 physically prevents the association between TRIF and TBK1. Taken together, these results demonstrate that TRIF associates with TRAF6 and TBK1 independently, and activates two distinct transcription factors, NF-κB and IFN regulatory factor-3, respectively.

Bibliography

Sato, S., Sugiyama, M., Yamamoto, M., Watanabe, Y., Kawai, T., Takeda, K., & Akira, S. (2003). Toll/IL-1 Receptor Domain-Containing Adaptor Inducing IFN-Î² (TRIF) Associates with TNF Receptor-Associated Factor 6 and TANK-Binding Kinase 1, and Activates Two Distinct Transcription Factors, NF-ÎºB and IFN-Regulatory Factor-3, in the Toll-Like Receptor Signaling. The Journal of Immunology, 171(8), 4304â4310.

Authors 7

Shintaro Sato (first)
Masanaka Sugiyama (additional)
Masahiro Yamamoto (additional)
Yasuyuki Watanabe (additional)
Taro Kawai (additional)
Kiyoshi Takeda (additional)
Shizuo Akira (additional)

References 23 Referenced 567

Dates

Type	When
Created	11 years, 4 months ago (April 20, 2014, 8:53 p.m.)
Deposited	7 months, 3 weeks ago (Jan. 2, 2025, 12:36 p.m.)
Indexed	2 weeks, 4 days ago (Aug. 5, 2025, 8:35 a.m.)
Issued	21 years, 10 months ago (Oct. 15, 2003)
Published	21 years, 10 months ago (Oct. 15, 2003)
Published Print	21 years, 10 months ago (Oct. 15, 2003)

Funders 0

None

BibTeX

@article{Sato_2003, title={Toll/IL-1 Receptor Domain-Containing Adaptor Inducing IFN-β (TRIF) Associates with TNF Receptor-Associated Factor 6 and TANK-Binding Kinase 1, and Activates Two Distinct Transcription Factors, NF-κB and IFN-Regulatory Factor-3, in the Toll-Like Receptor Signaling}, volume={171}, ISSN={1550-6606}, url={http://dx.doi.org/10.4049/jimmunol.171.8.4304}, DOI={10.4049/jimmunol.171.8.4304}, number={8}, journal={The Journal of Immunology}, publisher={Oxford University Press (OUP)}, author={Sato, Shintaro and Sugiyama, Masanaka and Yamamoto, Masahiro and Watanabe, Yasuyuki and Kawai, Taro and Takeda, Kiyoshi and Akira, Shizuo}, year={2003}, month=oct, pages={4304–4310} }

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  "abstract": "<jats:title>Abstract</jats:title>\n               <jats:p>We previously reported a new Toll/IL-1R (TIR)-containing molecule, named TIR domain-containing adaptor inducing IFN-\u03b2 (TRIF). Although initial study indicated that TRIF possesses the ability to activate not only the NF-\u03baB-dependent but also the IFN-\u03b2 promoters, the molecular mechanisms of TRIF-induced signaling are poorly understood. In this study, we investigated the signaling cascades through TRIF. TNF receptor-associated factor (TRAF)6 interacted with TRIF through the TRAF domain of TRAF6 and TRAF6-binding motifs found in the N-terminal portion of TRIF. Disruption of TRAF6-binding motifs of TRIF disabled it from associating with TRAF6, and resulted in a reduction in the TRIF-induced activation of the NF-\u03baB-dependent but not IFN-\u03b2 promoter. TANK-binding kinase (TBK)-1, which was recently reported to be a kinase of IFN regulatory factor-3, which is an essential transcription factor for IFN-\u03b2 expression, also associated with the N-terminal region of TRIF. Moreover, the association between TRIF and TBK1 appeared to require the kinase activity of TBK1, as well as phosphorylation of TRIF. Because TRAF6 and TBK1 bind close the region of TRIF, it seems that TRAF6 physically prevents the association between TRIF and TBK1. Taken together, these results demonstrate that TRIF associates with TRAF6 and TBK1 independently, and activates two distinct transcription factors, NF-\u03baB and IFN regulatory factor-3, respectively.</jats:p>",
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