Jens Randel Nyengaard

Attenuation of cGAS-STING signaling is mediated by a p62/SQSTM1-dependent autophagy pathway activated by TBK1

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Attenuation of cGAS-STING signaling is mediated by a p62/SQSTM1-dependent autophagy pathway activated by TBK1. / Prabakaran, Thaneas; Bodda, Chiranjeevi; Krapp, Christian; Zhang, Bao-Cun; Christensen, Maria H; Sun, Chenglong; Reinert, Line; Cai, Yujia; Jensen, Søren B; Skouboe, Morten K; Nyengaard, Jens R; Thompson, Craig B; Lebbink, Robert Jan; Sen, Ganes C; van Loo, Geert; Nielsen, Rikke; Komatsu, Masaaki; Nejsum, Lene N; Jakobsen, Martin R; Gyrd-Hansen, Mads; Paludan, Søren R.

In: E M B O Journal, Vol. 37, No. 8, E97858, 13.04.2018.

Research output: Contribution to journal/Conference contribution in journal/Contribution to newspaperJournal articleResearchpeer-review

Harvard

Prabakaran, T, Bodda, C, Krapp, C, Zhang, B-C, Christensen, MH, Sun, C, Reinert, L, Cai, Y, Jensen, SB, Skouboe, MK, Nyengaard, JR, Thompson, CB, Lebbink, RJ, Sen, GC, van Loo, G, Nielsen, R, Komatsu, M, Nejsum, LN, Jakobsen, MR, Gyrd-Hansen, M & Paludan, SR 2018, 'Attenuation of cGAS-STING signaling is mediated by a p62/SQSTM1-dependent autophagy pathway activated by TBK1', E M B O Journal, vol. 37, no. 8, E97858. https://doi.org/10.15252/embj.201797858

APA

CBE

Prabakaran T, Bodda C, Krapp C, Zhang B-C, Christensen MH, Sun C, Reinert L, Cai Y, Jensen SB, Skouboe MK, Nyengaard JR, Thompson CB, Lebbink RJ, Sen GC, van Loo G, Nielsen R, Komatsu M, Nejsum LN, Jakobsen MR, Gyrd-Hansen M, Paludan SR. 2018. Attenuation of cGAS-STING signaling is mediated by a p62/SQSTM1-dependent autophagy pathway activated by TBK1. E M B O Journal. 37(8):Article E97858. https://doi.org/10.15252/embj.201797858

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Author

Prabakaran, Thaneas ; Bodda, Chiranjeevi ; Krapp, Christian ; Zhang, Bao-Cun ; Christensen, Maria H ; Sun, Chenglong ; Reinert, Line ; Cai, Yujia ; Jensen, Søren B ; Skouboe, Morten K ; Nyengaard, Jens R ; Thompson, Craig B ; Lebbink, Robert Jan ; Sen, Ganes C ; van Loo, Geert ; Nielsen, Rikke ; Komatsu, Masaaki ; Nejsum, Lene N ; Jakobsen, Martin R ; Gyrd-Hansen, Mads ; Paludan, Søren R. / Attenuation of cGAS-STING signaling is mediated by a p62/SQSTM1-dependent autophagy pathway activated by TBK1. In: E M B O Journal. 2018 ; Vol. 37, No. 8.

Bibtex

@article{560f5be55bac4e0da64f5e2195ab6e37,
title = "Attenuation of cGAS-STING signaling is mediated by a p62/SQSTM1-dependent autophagy pathway activated by TBK1",
abstract = "Negative regulation of immune pathways is essential to achieve resolution of immune responses and to avoid excess inflammation. DNA stimulates type I IFN expression through the DNA sensor cGAS, the second messenger cGAMP, and the adaptor molecule STING Here, we report that STING degradation following activation of the pathway occurs through autophagy and is mediated by p62/SQSTM1, which is phosphorylated by TBK1 to direct ubiquitinated STING to autophagosomes. Degradation of STING was impaired in p62-deficient cells, which responded with elevated IFN production to foreign DNA and DNA pathogens. In the absence of p62, STING failed to traffic to autophagy-associated vesicles. Thus, DNA sensing induces the cGAS-STING pathway to activate TBK1, which phosphorylates IRF3 to induce IFN expression, but also phosphorylates p62 to stimulate STING degradation and attenuation of the response.",
author = "Thaneas Prabakaran and Chiranjeevi Bodda and Christian Krapp and Bao-Cun Zhang and Christensen, {Maria H} and Chenglong Sun and Line Reinert and Yujia Cai and Jensen, {S{\o}ren B} and Skouboe, {Morten K} and Nyengaard, {Jens R} and Thompson, {Craig B} and Lebbink, {Robert Jan} and Sen, {Ganes C} and {van Loo}, Geert and Rikke Nielsen and Masaaki Komatsu and Nejsum, {Lene N} and Jakobsen, {Martin R} and Mads Gyrd-Hansen and Paludan, {S{\o}ren R}",
note = "{\textcopyright} 2018 The Authors.",
year = "2018",
month = apr,
day = "13",
doi = "10.15252/embj.201797858",
language = "English",
volume = "37",
journal = "E M B O Journal",
issn = "0261-4189",
publisher = "Wiley-Blackwell Publishing Ltd.",
number = "8",

}

RIS

TY - JOUR

T1 - Attenuation of cGAS-STING signaling is mediated by a p62/SQSTM1-dependent autophagy pathway activated by TBK1

AU - Prabakaran, Thaneas

AU - Bodda, Chiranjeevi

AU - Krapp, Christian

AU - Zhang, Bao-Cun

AU - Christensen, Maria H

AU - Sun, Chenglong

AU - Reinert, Line

AU - Cai, Yujia

AU - Jensen, Søren B

AU - Skouboe, Morten K

AU - Nyengaard, Jens R

AU - Thompson, Craig B

AU - Lebbink, Robert Jan

AU - Sen, Ganes C

AU - van Loo, Geert

AU - Nielsen, Rikke

AU - Komatsu, Masaaki

AU - Nejsum, Lene N

AU - Jakobsen, Martin R

AU - Gyrd-Hansen, Mads

AU - Paludan, Søren R

N1 - © 2018 The Authors.

PY - 2018/4/13

Y1 - 2018/4/13

N2 - Negative regulation of immune pathways is essential to achieve resolution of immune responses and to avoid excess inflammation. DNA stimulates type I IFN expression through the DNA sensor cGAS, the second messenger cGAMP, and the adaptor molecule STING Here, we report that STING degradation following activation of the pathway occurs through autophagy and is mediated by p62/SQSTM1, which is phosphorylated by TBK1 to direct ubiquitinated STING to autophagosomes. Degradation of STING was impaired in p62-deficient cells, which responded with elevated IFN production to foreign DNA and DNA pathogens. In the absence of p62, STING failed to traffic to autophagy-associated vesicles. Thus, DNA sensing induces the cGAS-STING pathway to activate TBK1, which phosphorylates IRF3 to induce IFN expression, but also phosphorylates p62 to stimulate STING degradation and attenuation of the response.

AB - Negative regulation of immune pathways is essential to achieve resolution of immune responses and to avoid excess inflammation. DNA stimulates type I IFN expression through the DNA sensor cGAS, the second messenger cGAMP, and the adaptor molecule STING Here, we report that STING degradation following activation of the pathway occurs through autophagy and is mediated by p62/SQSTM1, which is phosphorylated by TBK1 to direct ubiquitinated STING to autophagosomes. Degradation of STING was impaired in p62-deficient cells, which responded with elevated IFN production to foreign DNA and DNA pathogens. In the absence of p62, STING failed to traffic to autophagy-associated vesicles. Thus, DNA sensing induces the cGAS-STING pathway to activate TBK1, which phosphorylates IRF3 to induce IFN expression, but also phosphorylates p62 to stimulate STING degradation and attenuation of the response.

U2 - 10.15252/embj.201797858

DO - 10.15252/embj.201797858

M3 - Journal article

C2 - 29496741

VL - 37

JO - E M B O Journal

JF - E M B O Journal

SN - 0261-4189

IS - 8

M1 - E97858

ER -