| Scientific background: |
TICAM1 (TIR DOMAIN-CONTAINING ADAPTOR MOLECULE 1), also known as TRIF, is an adapter in responding to activation of toll-like receptors (TLRs). It mediates the rather delayed cascade of two TLR-associated signaling cascades, where the other one is dependent upon a MyD88 adapter. By genomic sequence analysis, Oshiumi et al. (2003) mapped the TICAM1 gene to chromosome 19p13.3. By coimmunoprecipitation analysis, Oshiumi et al. (2003) showed that TICAM1 interacts specifically with TLR3, but not with other TLRs. Functional analysis showed that the association of TLR3 and TICAM1 mediates dsRNA activation of IFNB, through either NFKB, AP1, or IRF3. TICAM1 activation of NFKB was found to occur predominantly through IRAK1 rather than IRAK2 . Small interfering (si)RNA blockage of TICAM1, just upstream of the TIR domain, reduced IFNB production in response to dsRNA. |
| References: |
1. Carty, M., Goodbody, R., Schroder, M., Stack, J., Moynagh, P. N., Bowie, A. G.The human adaptor SARM negatively regulates adaptor protein TRIF-dependent Toll-like receptor signaling.Nature Immun. 7: 1074-1081, 2006.
2. Oshiumi, H., Matsumoto, M., Funami, K., Akazawa, T., Seya, T.TICAM-I, an adaptor molecule that participates in Toll-like receptor 3-mediated interferon-beta induction.Nature Immun. 4: 161-167, 2003.
3. Yamamoto, M., Sato, S., Mori, K., Hoshino, K., Takeuchi, O., Takeda, K., Akira, S.Cutting edge: a novel Toll/IL-1 receptor domain-containing adapter that preferentially activates the IFN-beta promoter in the Toll-like receptor signaling.J. Immun. 169: 6668-6672, 2002.
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