Role of the TAB2-related protein TAB3 in IL-1 and TNF signaling

Tohru Ishitani, Giichi Takaesu, Jun Ninomiya-Tsuji, Hiroshi Shibuya, Richard B. Gaynor, Kunihiro Matsumoto

Research output: Contribution to journalArticle

200 Citations (Scopus)

Abstract

The cytokines IL-1 and TNF induce expression of a series of genes that regulate inflammation through activation of NF-κB signal transduction pathways. TAK1, a MAPKKK, is critical for both IL-1- and TNF-induced activation of the NF-κB pathway. TAB2, a TAK1-binding protein, is involved in IL-1-induced NF-κB activation by physically linking TAK1 to TRAF6. However, IL-1-induced activation of NF-κB is not impaired in TAB2-deficient embryonic fibroblasts. Here we report the identification and characterization of a novel protein designated TAB3, a TAB2-like molecule that associates with TAK1 and can activate NF-κB similar to TAB2. Endogenous TAB3 interacts with TRAF6 and TRAF2 in an IL-1- and a TNF-dependent manner, respectively. Furthermore, IL-1 signaling leads to the ubiquitination of TAB2 and TAB3 through TRAF6. Cotransfection of siRNAs directed against both TAB2 and TAB3 inhibit both IL-1- and TNF-induced activation of TAK1 and NF-κB. These results suggest that TAB2 and TAB3 function redundantly as mediators of TAK1 activation in IL-1 and TNF signal transduction.

Original languageEnglish
Pages (from-to)6277-6288
Number of pages12
JournalEMBO Journal
Volume22
Issue number23
DOIs
Publication statusPublished - Dec 1 2003

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Interleukin-1
Chemical activation
TNF Receptor-Associated Factor 6
Proteins
Signal transduction
Signal Transduction
TNF Receptor-Associated Factor 2
MAP Kinase Kinase Kinases
Ubiquitination
Fibroblasts
Carrier Proteins
Genes
Cytokines
Inflammation
Molecules

All Science Journal Classification (ASJC) codes

  • Neuroscience(all)
  • Molecular Biology
  • Biochemistry, Genetics and Molecular Biology(all)
  • Immunology and Microbiology(all)

Cite this

Ishitani, T., Takaesu, G., Ninomiya-Tsuji, J., Shibuya, H., Gaynor, R. B., & Matsumoto, K. (2003). Role of the TAB2-related protein TAB3 in IL-1 and TNF signaling. EMBO Journal, 22(23), 6277-6288. https://doi.org/10.1093/emboj/cdg605

Role of the TAB2-related protein TAB3 in IL-1 and TNF signaling. / Ishitani, Tohru; Takaesu, Giichi; Ninomiya-Tsuji, Jun; Shibuya, Hiroshi; Gaynor, Richard B.; Matsumoto, Kunihiro.

In: EMBO Journal, Vol. 22, No. 23, 01.12.2003, p. 6277-6288.

Research output: Contribution to journalArticle

Ishitani, T, Takaesu, G, Ninomiya-Tsuji, J, Shibuya, H, Gaynor, RB & Matsumoto, K 2003, 'Role of the TAB2-related protein TAB3 in IL-1 and TNF signaling', EMBO Journal, vol. 22, no. 23, pp. 6277-6288. https://doi.org/10.1093/emboj/cdg605
Ishitani T, Takaesu G, Ninomiya-Tsuji J, Shibuya H, Gaynor RB, Matsumoto K. Role of the TAB2-related protein TAB3 in IL-1 and TNF signaling. EMBO Journal. 2003 Dec 1;22(23):6277-6288. https://doi.org/10.1093/emboj/cdg605
Ishitani, Tohru ; Takaesu, Giichi ; Ninomiya-Tsuji, Jun ; Shibuya, Hiroshi ; Gaynor, Richard B. ; Matsumoto, Kunihiro. / Role of the TAB2-related protein TAB3 in IL-1 and TNF signaling. In: EMBO Journal. 2003 ; Vol. 22, No. 23. pp. 6277-6288.
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