The cytokine-inducible zinc finger protein A20 inhibits IL-1-induced NF-kappa B activation at the level of TRAF6

The zinc finger protein A20 is encoded by an immediate early response gene whose expression is induced by different inflammatory stimuli, including in terleukin-1 (IL-1), Gene induction by IL-1 is mediated by activation of the transcription factor NF-kappa B, and requires the signal adapter protein T RAF6. The latter interacts with the NF-kappa B-inducing kinase NIK, which i s believed to be part of the I kappa B kinase complex, Expression of A20 po tently inhibits IL-1-induced NF-kappa B activation by an unknown mechanism. Inhibition of IL-1-induced NF-kappa B activation was found to be mediated by the C-terminal zinc finger-containing domain of A20. More importantly, w e present evidence that A20 interferes with IL-1-induced NF-kappa B activat ion at the level of TRAF6, upstream of NIK. Moreover, A20 was shown to dire ctly interact with TRAF6. (C) 1999 Federation of European Biochemical Socie ties.