TRAF6 is a signal transducer for interleukin-1

• Published in: Nature (London) 1996-10, Vol.383 (6599), p.443-446
• Main Authors: Cao, Zhaodan, Xiong, Jessie, Takeuchi, Masahiro, Kurama, Takeshi, Goeddel, David V.
• Format: Article
• Language: English
• Subjects: Amino Acid Sequence; Animals; Binding Sites; Carrier Proteins - genetics; Carrier Proteins - metabolism; Cell Line; Cells; Humanities and Social Sciences; Humans; Interleukin-1 - metabolism; Interleukin-1 Receptor-Associated Kinases; letter; Molecular biology; Molecular Sequence Data; multidisciplinary; NF-kappa B - metabolism; Protein Kinases - metabolism; Proteins; Science; Science (multidisciplinary); Sequence Deletion; Sequence Homology, Amino Acid; Signal Transduction; TNF Receptor-Associated Factor 6; Transducers; Transfection
• ISSN: 0028-0836; 1476-4687
• DOI: 10.1038/383443a0

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 superfamily 2–5 . 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 induction 6 . These findings indicate that TRAF proteins may function as signal transducers for distinct receptor families and that TRAF6 participates in IL-1 signalling.