Interleukin-1 receptor-associated kinase (IRAK) -1-mediated NF-kappaB activation requires cytosolic and nuclear activity.
Interleukin-1 receptor-associated kinase (IRAK) -1 plays an essential role in Toll-like receptor/interleukin-1 receptor (TLR/IL-1R) -associated NF-kappaB activation through its involvement in IKK activation, which then leads to subsequent IkappaB degradation and NF-kappaB nuclear translocation. In the present studies, we demonstrate a novel pathway in which IRAK-1 present in the nucleus ... participates in NF-kappaB-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-kappaB transcriptional activity that precedes IkappaB-alpha degradation and nuclear translocation of NF-kappaB. IRAK-1 binds to the promoter of NF-kappaB-regulated gene, IkappaB-alpha, and enhances binding of the NF-kappaB p65 subunit to NF-kappaB responsive elements within the IkappaB-alpha 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-kappaB-dependent transcriptional events.
Mesh Terms:
Animals, Base Sequence, Breast Neoplasms, Cell Line, Cell Line, Tumor, Cell Nucleus, Cytosol, DNA Primers, Female, Humans, Interleukin-1 Receptor-Associated Kinases, Kidney, Macrophages, Mice, Molecular Sequence Data, NF-kappa B, RNA, Messenger
Animals, Base Sequence, Breast Neoplasms, Cell Line, Cell Line, Tumor, Cell Nucleus, Cytosol, DNA Primers, Female, Humans, Interleukin-1 Receptor-Associated Kinases, Kidney, Macrophages, Mice, Molecular Sequence Data, NF-kappa B, RNA, Messenger
FASEB J.
Date: Jul. 01, 2008
PubMed ID: 18276832
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