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 |
|---|---|
| Pages (from-to) | 6277-6288 |
| Number of pages | 12 |
| Journal | EMBO Journal |
| Volume | 22 |
| Issue number | 23 |
| DOIs | |
| Publication status | Published - Dec 1 2003 |
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All Science Journal Classification (ASJC) codes
- Neuroscience(all)
- Molecular Biology
- Biochemistry, Genetics and Molecular Biology(all)
- Immunology and Microbiology(all)
Cite this
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 journal › Article
}
TY - JOUR
T1 - Role of the TAB2-related protein TAB3 in IL-1 and TNF signaling
AU - Ishitani, Tohru
AU - Takaesu, Giichi
AU - Ninomiya-Tsuji, Jun
AU - Shibuya, Hiroshi
AU - Gaynor, Richard B.
AU - Matsumoto, Kunihiro
PY - 2003/12/1
Y1 - 2003/12/1
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=0346243941&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0346243941&partnerID=8YFLogxK
U2 - 10.1093/emboj/cdg605
DO - 10.1093/emboj/cdg605
M3 - Article
C2 - 14633987
AN - SCOPUS:0346243941
VL - 22
SP - 6277
EP - 6288
JO - EMBO Journal
JF - EMBO Journal
SN - 0261-4189
IS - 23
ER -