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Figure 5 | Journal of Hematology & Oncology

Figure 5

From: MicroRNAs and Toll-like Receptor/Interleukin-1 Receptor Signaling

Figure 5

MyD88-independent TLR signaling . Particular TLRs, like TLR3 and TLR4, can initiate MyD88-independent signaling. Receptor activation leads to the association of TRIF (TIR-domain-containing adaptor protein inducing IFN-β) protein. Specific to TLR4 signaling, the adaptor protein TRAM (TRIF-related adaptor molecule) also associates with the receptor to facilitate TRIF binding. As a result of TRIF binding, downstream NF-κB-directed transcription occurs along with IFN-α/β production. Although the exact signaling chronology is undetermined, it is known that two non-canonical IKKs (inhibitor of NF-κB kinase complex), IKKε and TBK1 (TANK-binding kinase 1) are activated. As a result, theses IKKs can initiate both NF-κB and IRF-3 (interferon-3) activity. In addition to IRF-3, IRF-7 is also known to be activated in the independent pathway leading to IFN-α/β production.

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