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

Department of Molecular Biology, Flanders Interuniversity Institute for Biotechnology and University of Ghent, Belgium.
FEBS Letters (Impact Factor: 3.34). 02/1999; 442(2-3):147-50. DOI: 10.1016/S0014-5793(98)01645-7
Source: PubMed

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.

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