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J Biol Chem. 2011 Apr 15;286(15):12881-90. doi: 10.1074/jbc.M110.199547. Epub 2011 Feb 18.

IL-17-induced NF-kappaB activation via CIKS/Act1: physiologic significance and signaling mechanisms.

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1
Laboratory of Immunoregulation, NIAID, National Institutes of Health, Bethesda, Maryland 20852, USA.

Abstract

Interleukin-17 (IL-17) is essential in host defense against extracellular bacteria and fungi, especially at mucosal sites, but it also contributes significantly to inflammatory and autoimmune disease pathologies. Binding of IL-17 to its receptor leads to recruitment of adaptor protein CIKS/Act1 via heterotypic association of their respective SEFIR domains and activation of transcription factor NF-κB; it is not known whether CIKS and/or NF-κB are required for all gene induction events. Here we report that CIKS is essential for all IL-17-induced immediate-early genes in primary mouse embryo fibroblasts, whereas NF-κB is profoundly involved. We also identify a novel subdomain in the N terminus of CIKS that is essential for IL-17-mediated NF-κB activation. This domain is both necessary and sufficient for interaction between CIKS and TRAF6, an adaptor required for NF-κB activation. The ability of decoy peptides to block this interaction may provide a new therapeutic strategy for intervention in IL-17-driven autoimmune and inflammatory diseases.

PMID:
21335551
PMCID:
PMC3075635
DOI:
10.1074/jbc.M110.199547
[Indexed for MEDLINE]
Free PMC Article
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