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

The cytokines IL-1 and TNF induce expression of a series of genes that regulate inflammation through activation of NF-kappaB signal transduction pathways. TAK1, a MAPKKK, is critical for both IL-1- and TNF-induced activation of the NF-kappaB pathway. TAB2, a TAK1-binding protein, is involved in IL-1-induced NF-kappaB activation by physically linking ...
TAK1 to TRAF6. However, IL-1-induced activation of NF-kappaB 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-kappaB similar to TAB2. Endogenous TAB3 interacts with TRAF6 and TRAF2 in an IL-1- and a TNF-dependent manner, respectively. Further more, 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-kappaB. These results suggest that TAB2 and TAB3 function redundantly as mediators of TAK1 activation in IL-1 and TNF signal transduction.
Mesh Terms:
Adaptor Proteins, Signal Transducing, Amino Acid Sequence, Animals, Base Sequence, Carrier Proteins, Cloning, Molecular, DNA Primers, Drosophila, Humans, Inflammation, Interleukin-1, Intracellular Signaling Peptides and Proteins, Molecular Sequence Data, NF-kappa B, Proteins, Recombinant Proteins, Sequence Alignment, Sequence Homology, Amino Acid, Signal Transduction, TNF Receptor-Associated Factor 2, TNF Receptor-Associated Factor 6, Tumor Necrosis Factor-alpha
EMBO J.
Date: Dec. 01, 2003
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