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Regulation of Toll/IL-1-receptor-mediated gene expression by the inducible nuclear protein IκBζ

Yamamoto, Masahiro, Yamazaki, Soh, Uematsu, Satoshi, Sato, Shintaro, Hemmi, Hiroaki, Hoshino, Katsuaki, Kaisho, Tsuneyasu, Kuwata, Hirotaka, Takeuchi, Osamu, Takeshige, Koichiro, Saitoh, Tatsuya, Yamaoka, Shoji, Yamamoto, Naoki, Yamamoto, Shunsuke, Muta, Tatsushi, Takeda, Kiyoshi, Akira, Shizuo·2004·Nature
DOI 10.1038/nature02738
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Abstract

Toll-like receptors (TLRs) recognize microbial components and trigger the inflammatory and immune responses against pathogens. IkappaBzeta (also known as MAIL and INAP) is an ankyrin-repeat-containing nuclear protein that is highly homologous to the IkappaB family member Bcl-3 (refs 1-6). Transcription of IkappaBzeta is rapidly induced by stimulation with TLR ligands and interleukin-1 (IL-1). Here we show that IkappaBzeta is indispensable for the expression of a subset of genes activated in TLR/IL-1R signalling pathways. IkappaBzeta-deficient cells show severe impairment of IL-6 production in response to a variety of TLR ligands as well as IL-1, but not in response to tumour-necrosis factor-alpha. Endogenous IkappaBzeta specifically associates with the p50 subunit of NF-kappaB, and is recruited to the NF-kappaB binding site of the IL-6 promoter on stimulation. Moreover, NF-kappaB1/p50-deficient mice show responses to TLR/IL-1R ligands similar to those of IkappaBzeta-deficient mice. Endotoxin-induced expression of other genes such as Il12b and Csf2 is also abrogated in IkappaBzeta-deficient macrophages. Given that the lipopolysaccharide-induced transcription of IkappaBzeta occurs earlier than transcription of these genes, some TLR/IL-1R-mediated responses may be regulated in a gene expression process of at least two steps that requires inducible IkappaBzeta.

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Crossref · 10.1038/nature02738

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Research works printed but not linked: 24

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Metadata

Authors
Yamamoto, M., Yamazaki, S., Uematsu, S., Sato, S., Hemmi, H., Hoshino, K., Kaisho, T., Kuwata, H., Takeuchi, O., Takeshige, K., Saitoh, T., Yamaoka, S., Yamamoto, N., Yamamoto, S., Muta, T., Takeda, K., & Akira, S.
Venue
Nature
Publisher
Springer Science and Business Media LLC
Published
2004-07
Volume
430
Issue
6996
Pages
218-222
ISSN
  • 0028-0836
  • 1476-4687
DOI
10.1038/nature02738
Cited by
460
References
6
Language
en
Licence
www.springer.com/tdm (tdm)

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CoChat. (2026). Citation check: Regulation of Toll/IL-1-receptor-mediated gene expression by the inducible nuclear protein IκBζ. https://app.cochat.ai/papers/10.1038/nature02738
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Yamamoto, M., Yamazaki, S., Uematsu, S., Sato, S., Hemmi, H., Hoshino, K., Kaisho, T., Kuwata, H., Takeuchi, O., Takeshige, K., Saitoh, T., Yamaoka, S., Yamamoto, N., Yamamoto, S., Muta, T., Takeda, K., & Akira, S. (2004). Regulation of Toll/IL-1-receptor-mediated gene expression by the inducible nuclear protein IκBζ. Nature. https://doi.org/10.1038/nature02738