STRAP positively regulates TLR3-triggered signaling pathway

Hyunbin D. Huh, Eunhye Lee, Jinwook Shin, Boyoun Park, Sungwook Lee

Research output: Contribution to journalArticlepeer-review

4 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)55-60
Number of pages6
JournalCellular Immunology
Volume318
DOIs
Publication statusPublished - 2017 Aug

Bibliographical note

Funding 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.

Funding 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.

Publisher Copyright:
© 2017 Elsevier Inc.

All Science Journal Classification (ASJC) codes

  • Immunology

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