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

Abstract

The zinc finger protein A20 is encoded by an immediate early response gene whose expression is induced by different inflammatory stimuli, including interleukin-1 (IL-1). Gene induction by IL-1 is mediated by activation of the transcription factor NF-kappaB, and requires the signal adapter protein TRAF6. The latter interacts with the NF-kappaB-inducing kinase NIK, which is believed to be part of the IkappaB kinase complex. Expression of A20 potently inhibits IL-1-induced NF-kappaB activation by an unknown mechanism. Inhibition of IL-1-induced NF-kappaB activation was found to be mediated by the C-terminal zinc finger-containing domain of A20. More importantly, we present evidence that A20 interferes with IL-1-induced NF-kappaB activation at the level of TRAF6, upstream of NIK. Moreover, A20 was shown to directly interact with TRAF6.