Premium
Interleukin‐1 receptor‐associated kinase (IRAK) ‐1‐ mediated NF‐κ activation requires cytosolic and nuclear activity
Author(s) -
Liu Gang,
Park Young-Jun,
Abraham Edward
Publication year - 2008
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fj.07-101816
Subject(s) - cytosol , iκb kinase , phosphorylation , kinase , nf κb , microbiology and biotechnology , biology , signal transduction , nuclear receptor , transcription factor , gene , biochemistry , enzyme
Interleukin‐1 receptor‐associated kinase (IRAK) ‐1 plays an essential role in Toll‐like receptor/interleukin‐1 receptor (TLR/IL‐1R) ‐associated NF‐κB activation through its involvement in IKK activation, which then leads to subsequent IκB degradation and NF‐ k B nuclear translocation. In the present studies, we demonstrate a novel pathway in which IRAK‐1 present in the nucleus participates in NF‐κB‐dependent gene expression. Nuclear localization of IRAK‐1 is increased on cellular stimulation with IL‐1 and LPS, or CRM‐1‐dependent nuclear export blockade. Induction of IRAK‐1 produces enhanced NF‐ k B transcriptional activity that precedes IκB‐α degradation and nuclear translocation of NF‐κB. IRAK‐1 binds to the promoter of NF‐KB‐regulated gene, I κ B‐ α, and enhances binding of the NF‐κB p65 subunit to NF‐κB responsive elements within the I κ B‐ α promoter. IRAK‐1 phosphorylates histone H3 in vitro and is required for IL‐1‐induced phosphorylation of histone H3 at serine 10 in vivo. These data indicate that both cytosolic and nuclear actions of IRAK‐1 participate in the activation of NF‐ κB‐dependent transcriptional events.—Liu, G., Park, Y.‐J., Abraham, E. Interleukin‐1 receptor‐associated kinase (IRAK) ‐1‐mediated NF‐κB activation requires cytosolic and nuclear activity. FASEB J. 22, 2285–2296 (2008)