Toll-like receptor (TLR) signaling drives the innate immune response by activating nuclear factor-κB (NF-κB) and interferon regulatory factor (IRF). We have previously shown that STRAP interacts with TAK1 and IKKα along with NF-κB subunit p65, leading to the activation of pro-inflammatory cytokines. However, the roles of STRAP in TRIF/TBK1-mediated TLR3 activation and the subsequent type I interferon (IFN) production are not fully elucidated. Here, we demonstrate that STRAP acts as a scaffold protein in TLR3-triggered signaling. STRAP strongly interacts with TBK1 and IRF3, which enhances IFN-β production. As a consequence, STRAP knockdown reduces the level of both pro-inflammatory cytokine and IFN in TLR3 agonist-stimulated macrophages, whereas its overexpression significantly enhances production of these cytokines. Furthermore, the C-terminus of STRAP is essential for its functional activity in TLR3-mediated IL-6 and IFN-β production. These data suggest that STRAP is a positive regulator of the TLR3-meditated NF-κB and IRF signaling pathway.
Bibliographical noteFunding Information:
This study was supported by grants from the Korean Health Technology R&D Project, Ministry of Health & Welfare, Republic of Korea ( HI14C2542 ), and from the Basic Science Research Program through the National Research Foundation of Korea (NRF) funded by the Ministry of Science, ICT, and future planning (MSIP) ( 2015R1A2A1A15055053 and 2015R1D1A1A02062058 ). This work was also supported by the National Research Foundation of Korea (NRF) grant funded by the Korean Government ( MSIP ) ( NRF-2016R1A5A1010764 ), and by the Strategic Initiative for Microbiomes in Agriculture and Food funded by Ministry of Agriculture, Food and Rural Affairs ( 916006-2 ). S.L. was supported by Basic Science Research Program through the National Research Foundation of Korea (NRF) funded by the Ministry of Education ( 2015R1D1A1A01060181 ) and a research grant from the National Cancer Center of Korea ( NCC-1710210 ). H.D.H was supported by the Brain Korea (BK21) PLUS Program.
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