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The cytokine‐inducible zinc finger protein A20 inhibits IL‐1‐induced NF‐κB activation at the level of TRAF6
Author(s) -
Heyninck Karen,
Beyaert Rudi
Publication year - 1999
Publication title -
febs letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.593
H-Index - 257
eISSN - 1873-3468
pISSN - 0014-5793
DOI - 10.1016/s0014-5793(98)01645-7
Subject(s) - zinc finger , signal transducing adaptor protein , signal transduction , chemistry , nf κb , transcription factor , microbiology and biotechnology , kinase , nfkb1 , biology , gene , biochemistry
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‐κB, and requires the signal adapter protein TRAF6. The latter interacts with the NF‐κB‐inducing kinase NIK, which is believed to be part of the IκB kinase complex. Expression of A20 potently inhibits IL‐1‐induced NF‐κB activation by an unknown mechanism. Inhibition of IL‐1‐induced NF‐κB 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‐κB activation at the level of TRAF6, upstream of NIK. Moreover, A20 was shown to directly interact with TRAF6.