Abstract
MANY cytokines signal through different cell-surface receptors to activate the transcription factor NF-κB (ref. 1). Members of the TRAF protein family have been implicated in the activation of NF-κB by the tumour-necrosis factor (TNF)-receptor superfamily2–5. Here we report the identification of a new TRAF family member, designated TRAF6. When overexpressed in human 293 cells, TRAF6 activates NF-κB. A dominant-negative mutant of TRAF6 inhibits NF-κB activation signalled by interleukin-1 (IL-1) but not by TNF. IL-1 treatment of 293 cells induces the association of TRAF6 with IRAK, a serine/threonine kinase that is rapidly recruited to the IL-1 receptor after IL-1 induction6. These findings indicate that TRAF proteins may function as signal transducers for distinct receptor families and that TRAF6 participates in IL-1 signalling.
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References
Baeuerle, P. A. & Henkel, T. Annu. Rev. Immunol. 12, 141–179 (1994).
Rothe, M., Sarma, V., Dixit, V. M. & Goeddel, D. V. Science 269, 1424–1427 (1995).
Hsu, H., Shu, H. B., Pan, M. G. & Goeddel, D. V. Cell 84, 299–308 (1996).
Nakano, H. et al. J. Biol. Chem. 271, 14661–14664 (1996).
Takeuchi, M., Rothe, M. & Goeddel, D. V. J. Biol. Chem. 271, 19935–19942 (1996).
Cao, Z., Henzel, W. J. & Gao, X. Science 271, 1128–1131 (1996).
McDonald, P. P. et al. Eur. J. Immunol. 25, 2870–2876 (1995).
Berberich, I., Shu, G. L. & Clark, E. A. J. Immunol. 153, 4357–4366 (1994).
Sarma, V. et al. J. Biol. Chem. 270, 12343–12346 (1995).
Messer, G., Weiss, E. H. & Baeuerle, P. A. Cytokine 2, 389–397 (1990).
Gruss, H.-J. & Dower, S. K. Blood 85, 3378–3404 (1995).
Dinarello, C. Blood 87, 2095–2147 (1996).
Ulevitch, R. J. & Tobias, P. S. Annu. Rev. Immunol. 13, 437–457 (1995).
Rothe, M., Wong, S. C., Henzel, W. J. & Goeddel, D. V. Cell 78, 681–692 (1994).
Cheng, G. et al. Science 267, 1494–1498 (1995).
Hu, H. M., O'Rourke, K., Boguski, M. S. & Dixit, V. M. J. Biol. Chem. 269, 30069–30072 (1994).
Mosialos, G. et al. Cell 80, 389–399 (1995).
Sato, T., Irie, S. & Reed, J. C. FEBS Lett. 358, 113–118 (1995).
Song, H. Y. & Donner, D. B. Biochem. J. 309, 825–829 (1995).
Shelton, C. A. & Wasserman, S. A. Cell 72, 515–525 (1993).
Hsu, H., Huang, J., Shu, H.-B., Baichwal, V. & Goeddel, D. V. Immunity 4, 387–396 (1996).
Rothe, M., Pan, M.-G., Henzel, W. J., Ayres, T. M. & Goeddel, D. V. Cell 83, 1243–1252 (1995).
Schall, T. J. et al. Cell 61, 361–370 (1990).
Ausubel, F. M. et al. Curr. Prot. Mol. Biol. 1, 9.1.1–9.1.3 (1994).
Schütze, S. et al. Cell 71, 765–776 (1992).
Schindler, U. & Baichwal, V. R. Mol. Cell. Biol. 14, 5820–5831 (1994).
Croston, G. E., Cao, Z. & Goeddel, D. V. J. Biol. Chem. 270, 16514–16517 (1995).
Regnier, C. H. et al. J. Biol. Chem. 270, 25715–25721 (1995).
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Cao, Z., Xiong, J., Takeuchi, M. et al. TRAF6 is a signal transducer for interleukin-1. Nature 383, 443–446 (1996). https://doi.org/10.1038/383443a0
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DOI: https://doi.org/10.1038/383443a0
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