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B activation requires cytosolic and nuclear activity
E-mail contact: eabraham@uab.edu
Interleukin-1 receptor-associated kinase (IRAK)-1 plays an essential role in Toll-like receptor/interleukin-1 receptor (TLR/IL-1R) -associated NF-
B activation through its involvement in IKK activation, which then leads to subsequent I
B degradation and NF-
B nuclear translocation. In the present studies, we demonstrate a novel pathway in which IRAK-1 present in the nucleus participates in NF-
B-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-
B transcriptional activity that precedes I
B-
degradation and nuclear translocation of NF-
B. IRAK-1 binds to the promoter of NF-
B-regulated gene, I
B-
, and enhances binding of the NF-
B p65 subunit to NF-
B responsive elements within the I
B-
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-
B-dependent transcriptional events.—Liu, G., Park, Y.-J., Abraham, E. Interleukin-1 receptor-associated kinase (IRAK)-1-mediated NF-
B activation requires cytosolic and nuclear activity.
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