STRAP positively regulates TLR3-triggered signaling pathway

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

doi:10.1016/j.cellimm.2017.06.005

STRAP positively regulates TLR3-triggered signaling pathway

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

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7 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 language	English
Pages (from-to)	55-60
Number of pages	6
Journal	Cellular Immunology
Volume	318
DOIs	https://doi.org/10.1016/j.cellimm.2017.06.005
Publication status	Published - 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.

Publisher Copyright:
© 2017 Elsevier Inc.

All Science Journal Classification (ASJC) codes

Immunology

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10.1016/j.cellimm.2017.06.005

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@article{893f8ceae2854ad0b0d00130a1521703,

title = "STRAP positively regulates TLR3-triggered signaling pathway",

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.",

author = "Huh, {Hyunbin D.} and Eunhye Lee and Jinwook Shin and Boyoun Park and Sungwook Lee",

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. Publisher Copyright: {\textcopyright} 2017 Elsevier Inc.",

year = "2017",

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doi = "10.1016/j.cellimm.2017.06.005",

language = "English",

volume = "318",

pages = "55--60",

journal = "Cellular Immunology",

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AU - Huh, Hyunbin D.

AU - Lee, Eunhye

AU - Shin, Jinwook

AU - Park, Boyoun

AU - Lee, Sungwook

N1 - 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.

PY - 2017/8

Y1 - 2017/8

N2 - 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.

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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DO - 10.1016/j.cellimm.2017.06.005

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AN - SCOPUS:85021254122

SN - 0008-8749

VL - 318

SP - 55

EP - 60

JO - Cellular Immunology

JF - Cellular Immunology

ER -

STRAP positively regulates TLR3-triggered signaling pathway

Abstract

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