STRAP positively regulates TLR3-triggered signaling pathway

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

Research output: Contribution to journalArticle

1 Citation (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

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Interferon Regulatory Factors
Interferons
Cytokines
Interferon Type I
Toll-Like Receptors
Innate Immunity
Interleukin-6
Macrophages
Proteins

All Science Journal Classification (ASJC) codes

  • Immunology

Cite this

Huh, Hyunbin D. ; Lee, Eunhye ; Shin, Jinwook ; Park, Boyoun ; Lee, Sungwook. / STRAP positively regulates TLR3-triggered signaling pathway. In: Cellular Immunology. 2017 ; Vol. 318. pp. 55-60.
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STRAP positively regulates TLR3-triggered signaling pathway. / Huh, Hyunbin D.; Lee, Eunhye; Shin, Jinwook; Park, Boyoun; Lee, Sungwook.

In: Cellular Immunology, Vol. 318, 08.2017, p. 55-60.

Research output: Contribution to journalArticle

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AB - 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.

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