Journal
JOURNAL OF IMMUNOLOGY
Volume 174, Issue 1, Pages 27-30Publisher
AMER ASSOC IMMUNOLOGISTS
DOI: 10.4049/jimmunol.174.1.27
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TLRs signal the presence of microbial patterns and activate transcription factors. In TLR3 and TLR4, the adapter Toll-IL-1R homology domain-containing adapter molecule (TICAM-1) (also called Toll/IL-1R domain-containing adapter inducing IFN-beta (TRIF)) mediates IFN regulatory factor 3 (IRF3) phosphorylation followed by IFN-beta production. The regulatory subunit TNFR-associated factor family member-associated NF-kappaB activator (TANK) couples with the kinase complex IkappaB kinase-related kinase epsilon/NF-kappaB-activating kinase (NAK) (TANK-hinding kinase 1 (TBK1)) that involve TICAM-1-dependent IFN-beta induction. There are several TANK-homologous proteins. We tested whether TICAM-1 binds and coprecipitates with TANK or its family proteins. The results are: 1) the TANK family protein NAK-associated protein 1 (NAP1), but not TANK, coprecipitates with TICAM-1; 2) NAP1 overexpression markedly enhances TBK1-mediated IFN-beta promoter activation; 3) a dominant-negative form, NAP (158-270), suppresses IRF3 activation in response to poly(I:C) or LPS; 4) RNA interference targeting of the NAP1 message results in a failure of poly(L Q-mediated IRF3 polymerization and IFN-beta production. Thus, NAP1 is the kinase subunit responsible for TLR3/4-mediated IFN-beta induction in the TIC4M-1 pathway.
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