TBK1-associated Protein in Endolysosomes (TAPE) is an innate immune regulator modulating the TLR3 and TLR4 signaling pathways

Chun Hung Chang, Li Chun Lai, Hung Chi Cheng, Kuan Ru Chen, Ying Zhang Syue, Hsueh Chi Lu, Wan Ying Lin, Shun Hua Chen, Huei Sheng Huang, Ai Li Shiau, Huan Yao Lei, Jun Qin, Pin Ling

研究成果: Article

18 引文 (Scopus)

摘要

The innate immune system elicits the first wave of immune responses against pathogen infection. Its operational modes are complex and have yet to be defined. Here, we report the identification of an innate immune regulator termed TAPE (TBK1-associated protein in endolysosomes), previously known as CC2D1A/Freud-1/Aki-1, which modulates the TLR3 and TLR4 pathways.Wefound that TAPE activated the TBK1, NF-κB, and ERK pathways leading to IFN-β and inflammatory cytokine induction. TAPE was shown to colocalize with endosomal marker Rab5 and lysosomal marker LAMP1 in mammalian cells, suggesting that TAPE resided in endolysosomes. Knockdown of TAPE selectively impaired the TLR3 and endocytic TLR4 pathways to IFN-β induction. Furthermore, TAPE interacted and synergized with Trif to activate IFN-β. TAPE knockdown failed to block Trif-mediated IFN-β induction, whereas Trif knockdown impaired the TLR3 and TAPE cooperation on IFN-β induction, suggesting that TAPE acts upstream of Trif. Together, our data demonstrate a central role for TAPE in linking TLR3 and TLR4 to innate immune defenses at an early step.

原文English
頁(從 - 到)7043-7051
頁數9
期刊Journal of Biological Chemistry
286
發行號9
DOIs
出版狀態Published - 2011 三月 4

指紋

Proteins
MAP Kinase Signaling System
Immune system
Pathogens
Immune System
Cells
Cytokines
Infection

All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Molecular Biology
  • Cell Biology

引用此文

@article{45ed79584b164980941366f63e2ec5a6,
title = "TBK1-associated Protein in Endolysosomes (TAPE) is an innate immune regulator modulating the TLR3 and TLR4 signaling pathways",
abstract = "The innate immune system elicits the first wave of immune responses against pathogen infection. Its operational modes are complex and have yet to be defined. Here, we report the identification of an innate immune regulator termed TAPE (TBK1-associated protein in endolysosomes), previously known as CC2D1A/Freud-1/Aki-1, which modulates the TLR3 and TLR4 pathways.Wefound that TAPE activated the TBK1, NF-κB, and ERK pathways leading to IFN-β and inflammatory cytokine induction. TAPE was shown to colocalize with endosomal marker Rab5 and lysosomal marker LAMP1 in mammalian cells, suggesting that TAPE resided in endolysosomes. Knockdown of TAPE selectively impaired the TLR3 and endocytic TLR4 pathways to IFN-β induction. Furthermore, TAPE interacted and synergized with Trif to activate IFN-β. TAPE knockdown failed to block Trif-mediated IFN-β induction, whereas Trif knockdown impaired the TLR3 and TAPE cooperation on IFN-β induction, suggesting that TAPE acts upstream of Trif. Together, our data demonstrate a central role for TAPE in linking TLR3 and TLR4 to innate immune defenses at an early step.",
author = "Chang, {Chun Hung} and Lai, {Li Chun} and Cheng, {Hung Chi} and Chen, {Kuan Ru} and Syue, {Ying Zhang} and Lu, {Hsueh Chi} and Lin, {Wan Ying} and Chen, {Shun Hua} and Huang, {Huei Sheng} and Shiau, {Ai Li} and Lei, {Huan Yao} and Jun Qin and Pin Ling",
year = "2011",
month = "3",
day = "4",
doi = "10.1074/jbc.M110.164632",
language = "English",
volume = "286",
pages = "7043--7051",
journal = "Journal of Biological Chemistry",
issn = "0021-9258",
publisher = "American Society for Biochemistry and Molecular Biology Inc.",
number = "9",

}

TBK1-associated Protein in Endolysosomes (TAPE) is an innate immune regulator modulating the TLR3 and TLR4 signaling pathways. / Chang, Chun Hung; Lai, Li Chun; Cheng, Hung Chi; Chen, Kuan Ru; Syue, Ying Zhang; Lu, Hsueh Chi; Lin, Wan Ying; Chen, Shun Hua; Huang, Huei Sheng; Shiau, Ai Li; Lei, Huan Yao; Qin, Jun; Ling, Pin.

於: Journal of Biological Chemistry, 卷 286, 編號 9, 04.03.2011, p. 7043-7051.

研究成果: Article

TY - JOUR

T1 - TBK1-associated Protein in Endolysosomes (TAPE) is an innate immune regulator modulating the TLR3 and TLR4 signaling pathways

AU - Chang, Chun Hung

AU - Lai, Li Chun

AU - Cheng, Hung Chi

AU - Chen, Kuan Ru

AU - Syue, Ying Zhang

AU - Lu, Hsueh Chi

AU - Lin, Wan Ying

AU - Chen, Shun Hua

AU - Huang, Huei Sheng

AU - Shiau, Ai Li

AU - Lei, Huan Yao

AU - Qin, Jun

AU - Ling, Pin

PY - 2011/3/4

Y1 - 2011/3/4

N2 - The innate immune system elicits the first wave of immune responses against pathogen infection. Its operational modes are complex and have yet to be defined. Here, we report the identification of an innate immune regulator termed TAPE (TBK1-associated protein in endolysosomes), previously known as CC2D1A/Freud-1/Aki-1, which modulates the TLR3 and TLR4 pathways.Wefound that TAPE activated the TBK1, NF-κB, and ERK pathways leading to IFN-β and inflammatory cytokine induction. TAPE was shown to colocalize with endosomal marker Rab5 and lysosomal marker LAMP1 in mammalian cells, suggesting that TAPE resided in endolysosomes. Knockdown of TAPE selectively impaired the TLR3 and endocytic TLR4 pathways to IFN-β induction. Furthermore, TAPE interacted and synergized with Trif to activate IFN-β. TAPE knockdown failed to block Trif-mediated IFN-β induction, whereas Trif knockdown impaired the TLR3 and TAPE cooperation on IFN-β induction, suggesting that TAPE acts upstream of Trif. Together, our data demonstrate a central role for TAPE in linking TLR3 and TLR4 to innate immune defenses at an early step.

AB - The innate immune system elicits the first wave of immune responses against pathogen infection. Its operational modes are complex and have yet to be defined. Here, we report the identification of an innate immune regulator termed TAPE (TBK1-associated protein in endolysosomes), previously known as CC2D1A/Freud-1/Aki-1, which modulates the TLR3 and TLR4 pathways.Wefound that TAPE activated the TBK1, NF-κB, and ERK pathways leading to IFN-β and inflammatory cytokine induction. TAPE was shown to colocalize with endosomal marker Rab5 and lysosomal marker LAMP1 in mammalian cells, suggesting that TAPE resided in endolysosomes. Knockdown of TAPE selectively impaired the TLR3 and endocytic TLR4 pathways to IFN-β induction. Furthermore, TAPE interacted and synergized with Trif to activate IFN-β. TAPE knockdown failed to block Trif-mediated IFN-β induction, whereas Trif knockdown impaired the TLR3 and TAPE cooperation on IFN-β induction, suggesting that TAPE acts upstream of Trif. Together, our data demonstrate a central role for TAPE in linking TLR3 and TLR4 to innate immune defenses at an early step.

UR - http://www.scopus.com/inward/record.url?scp=79953200483&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=79953200483&partnerID=8YFLogxK

U2 - 10.1074/jbc.M110.164632

DO - 10.1074/jbc.M110.164632

M3 - Article

C2 - 21189260

AN - SCOPUS:79953200483

VL - 286

SP - 7043

EP - 7051

JO - Journal of Biological Chemistry

JF - Journal of Biological Chemistry

SN - 0021-9258

IS - 9

ER -