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 language | English |
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Pages (from-to) | 6277-6288 |
Number of pages | 12 |
Journal | EMBO Journal |
Volume | 22 |
Issue number | 23 |
DOIs | |
Publication status | Published - Dec 1 2003 |
Externally published | Yes |
All Science Journal Classification (ASJC) codes
- Neuroscience(all)
- Molecular Biology
- Biochemistry, Genetics and Molecular Biology(all)
- Immunology and Microbiology(all)