TAK1-binding protein 2 facilitates ubiquitination of TRAF6 and assembly of TRAF6 with IKK in the IL-1 signaling pathway.
TAK1 mitogen-activated protein kinase kinase kinase participates in the Interleukin-1 (IL-1) signaling pathway by mediating activation of JNK, p38, and NF-kappaB. TAK1-binding protein 2 (TAB2) was previously identified as an adaptor that links TAK1 to an upstream signaling intermediate, tumor necrosis factor receptor-associated factor 6 (TRAF6). Recently, ubiquitination of TRAF6 was shown to play an essential role in the activation of TAK1. However, the mechanism by which IL-1 induces TRAF6 ubiquitination remains to be elucidated. Here we report that TAB2 functions to facilitate TRAF6 ubiquitination and thereby mediates IL-1-induced cellular events. A conserved ubiquitin binding domain in TAB2, the CUE domain, is important for this function. We also found that TAB2 promotes the assembly of TRAF6 with a downstream kinase, IkappaB kinase (IKK). These results show that TAB2 acts as a multifunctional signaling molecule, facilitating both IL-1-dependent TRAF6 ubiquitination and assembly of the IL-1 signaling complex.
Kishida
Satoshi
S
Department of Molecular Biology, Graduate School of Science, Nagoya University, Nagoya, 464-8602 Japan.
Sanjo
Hideki
H
Akira
Shizuo
S
Matsumoto
Kunihiro
K
Ninomiya-Tsuji
Jun
J
D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D051550:I-kappa B Kinase; D007375:Interleukin-1 / Q000378:metabolism*; D051379:Mice; D009154:Mutation; D016328:NF-kappa B / Q000378:metabolism; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism*; D017434:Protein Structure, Tertiary; D015398:Signal Transduction / Q000502:physiology; D048029:TNF Receptor-Associated Factor 6 / Q000378:metabolism*; D025801:Ubiquitin / Q000378:metabolism*
D048868:Adaptor Proteins, Signal Transducing; D007375:Interleukin-1; D016328:NF-kappa B; D048029:TNF Receptor-Associated Factor 6; C498761:Tab2 protein, mouse; D025801:Ubiquitin; D017346:Protein Serine-Threonine Kinases; C496564:Chuk protein, mouse; D051550:I-kappa B Kinase; C496562:Ikbkb protein, mouse; C496566:Ikbke protein, mouse