MANY cytokines signal through different cell-surface receptors to activate the transcription factor NF-kappa B (ref. 1). Members of the TRAF protein family have been implicated in the activation of NF-kappa B 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-kappa B. A dominant-negative mutant of TRAF6 inhibits NF-kappa B 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.