The cytokine-inducible zinc finger protein A20 inhibits IL-1-induced NF-kappaB 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 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.
Mesh Terms:
Blotting, Western, Cell Line, Gene Expression Regulation, Humans, Interleukin-1, Intracellular Signaling Peptides and Proteins, Kidney, NF-kappa B, Nuclear Proteins, Precipitin Tests, Protein-Serine-Threonine Kinases, Proteins, Sequence Deletion, Signal Transduction, TNF Receptor-Associated Factor 1, TNF Receptor-Associated Factor 2, TNF Receptor-Associated Factor 6, Transcriptional Activation, Transfection, Tumor Necrosis Factor-alpha, Zinc Fingers
Blotting, Western, Cell Line, Gene Expression Regulation, Humans, Interleukin-1, Intracellular Signaling Peptides and Proteins, Kidney, NF-kappa B, Nuclear Proteins, Precipitin Tests, Protein-Serine-Threonine Kinases, Proteins, Sequence Deletion, Signal Transduction, TNF Receptor-Associated Factor 1, TNF Receptor-Associated Factor 2, TNF Receptor-Associated Factor 6, Transcriptional Activation, Transfection, Tumor Necrosis Factor-alpha, Zinc Fingers
FEBS Lett.
Date: Jan. 15, 1999
PubMed ID: 9928991
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