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

研究成果: ジャーナルへの寄稿記事

202 引用 (Scopus)


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.

ジャーナルEMBO Journal
出版物ステータス出版済み - 12 1 2003


All Science Journal Classification (ASJC) codes

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


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.