Human ZBP1 induces cell death-independent inflammatory signaling via RIPK3 and RIPK1

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Human ZBP1 induces cell death-independent inflammatory signaling via RIPK3 and RIPK1. / Peng, Ruoshi; Wang, Chris Kedong; Wang-Kan, Xuan; Idorn, Manja; Kjær, Majken; Zhou, Felix Y.; Fiil, Berthe Katrine; Timmermann, Frederik; Orozco, Susana L.; McCarthy, Julia; Leung, Carol S.; Lu, Xin; Bagola, Katrin; Rehwinkel, Jan; Oberst, Andrew; Maelfait, Jonathan; Paludan, Søren R.; Gyrd-Hansen, Mads.

In: EMBO Reports, Vol. 2022, No. 23, e55839, 2022.

Research output: Contribution to journal › Journal article › Research › peer-review

Harvard

Peng, R, Wang, CK, Wang-Kan, X, Idorn, M, Kjær, M, Zhou, FY, Fiil, BK, Timmermann, F, Orozco, SL, McCarthy, J, Leung, CS, Lu, X, Bagola, K, Rehwinkel, J, Oberst, A, Maelfait, J, Paludan, SR & Gyrd-Hansen, M 2022, 'Human ZBP1 induces cell death-independent inflammatory signaling via RIPK3 and RIPK1', EMBO Reports, vol. 2022, no. 23, e55839. https://doi.org/10.15252/embr.202255839

APA

Peng, R., Wang, C. K., Wang-Kan, X., Idorn, M., Kjær, M., Zhou, F. Y., Fiil, B. K., Timmermann, F., Orozco, S. L., McCarthy, J., Leung, C. S., Lu, X., Bagola, K., Rehwinkel, J., Oberst, A., Maelfait, J., Paludan, S. R., & Gyrd-Hansen, M. (2022). Human ZBP1 induces cell death-independent inflammatory signaling via RIPK3 and RIPK1. EMBO Reports, 2022(23), [e55839]. https://doi.org/10.15252/embr.202255839

Vancouver

Peng R, Wang CK, Wang-Kan X, Idorn M, Kjær M, Zhou FY et al. Human ZBP1 induces cell death-independent inflammatory signaling via RIPK3 and RIPK1. EMBO Reports. 2022;2022(23). e55839. https://doi.org/10.15252/embr.202255839

Author

Peng, Ruoshi ; Wang, Chris Kedong ; Wang-Kan, Xuan ; Idorn, Manja ; Kjær, Majken ; Zhou, Felix Y. ; Fiil, Berthe Katrine ; Timmermann, Frederik ; Orozco, Susana L. ; McCarthy, Julia ; Leung, Carol S. ; Lu, Xin ; Bagola, Katrin ; Rehwinkel, Jan ; Oberst, Andrew ; Maelfait, Jonathan ; Paludan, Søren R. ; Gyrd-Hansen, Mads. / Human ZBP1 induces cell death-independent inflammatory signaling via RIPK3 and RIPK1. In: EMBO Reports. 2022 ; Vol. 2022, No. 23.

Bibtex

@article{2b8863b52aca486594f7a0e34c023159,
title = "Human ZBP1 induces cell death-independent inflammatory signaling via RIPK3 and RIPK1",
abstract = "ZBP1 is an interferon-induced cytosolic nucleic acid sensor that facilitates antiviral responses via RIPK3. Although ZBP1-mediated programmed cell death is widely described, whether and how it promotes inflammatory signaling is unclear. Here, we report a ZBP1-induced inflammatory signaling pathway mediated by K63- and M1-linked ubiquitin chains, which depends on RIPK1 and RIPK3 as scaffolds independently of cell death. In human HT29 cells, ZBP1 associated with RIPK1 and RIPK3 as well as ubiquitin ligases cIAP1 and LUBAC. ZBP1-induced K63- and M1-linked ubiquitination of RIPK1 and ZBP1 to promote TAK1- and IKK-mediated inflammatory signaling and cytokine production. Inhibition of caspase activity suppressed ZBP1-induced cell death but enhanced cytokine production in a RIPK1- and RIPK3 kinase activity-dependent manner. Lastly, we provide evidence that ZBP1 signaling contributes to SARS-CoV-2-induced cytokine production. Taken together, we describe a ZBP1-RIPK3-RIPK1-mediated inflammatory signaling pathway relayed by the scaffolding role of RIPKs and regulated by caspases, which may induce inflammation when ZBP1 is activated below the threshold needed to trigger a cell death response.",
keywords = "inflammatory signaling, RIPK1, RIPK3, SARS-CoV-2, ZBP1",
author = "Ruoshi Peng and Wang, {Chris Kedong} and Xuan Wang-Kan and Manja Idorn and Majken Kj{\ae}r and Zhou, {Felix Y.} and Fiil, {Berthe Katrine} and Frederik Timmermann and Orozco, {Susana L.} and Julia McCarthy and Leung, {Carol S.} and Xin Lu and Katrin Bagola and Jan Rehwinkel and Andrew Oberst and Jonathan Maelfait and Paludan, {S{\o}ren R.} and Mads Gyrd-Hansen",
note = "Publisher Copyright: {\textcopyright} 2022 The Authors. Published under the terms of the CC BY 4.0 license.",
year = "2022",
doi = "10.15252/embr.202255839",
language = "English",
volume = "2022",
journal = "E M B O Reports",
issn = "1469-221X",
publisher = "Wiley-Blackwell",
number = "23",

}

RIS

TY - JOUR

T1 - Human ZBP1 induces cell death-independent inflammatory signaling via RIPK3 and RIPK1

AU - Peng, Ruoshi

AU - Wang, Chris Kedong

AU - Wang-Kan, Xuan

AU - Idorn, Manja

AU - Kjær, Majken

AU - Zhou, Felix Y.

AU - Fiil, Berthe Katrine

AU - Timmermann, Frederik

AU - Orozco, Susana L.

AU - McCarthy, Julia

AU - Leung, Carol S.

AU - Lu, Xin

AU - Bagola, Katrin

AU - Rehwinkel, Jan

AU - Oberst, Andrew

AU - Maelfait, Jonathan

AU - Paludan, Søren R.

AU - Gyrd-Hansen, Mads

N1 - Publisher Copyright: © 2022 The Authors. Published under the terms of the CC BY 4.0 license.

PY - 2022

Y1 - 2022

N2 - ZBP1 is an interferon-induced cytosolic nucleic acid sensor that facilitates antiviral responses via RIPK3. Although ZBP1-mediated programmed cell death is widely described, whether and how it promotes inflammatory signaling is unclear. Here, we report a ZBP1-induced inflammatory signaling pathway mediated by K63- and M1-linked ubiquitin chains, which depends on RIPK1 and RIPK3 as scaffolds independently of cell death. In human HT29 cells, ZBP1 associated with RIPK1 and RIPK3 as well as ubiquitin ligases cIAP1 and LUBAC. ZBP1-induced K63- and M1-linked ubiquitination of RIPK1 and ZBP1 to promote TAK1- and IKK-mediated inflammatory signaling and cytokine production. Inhibition of caspase activity suppressed ZBP1-induced cell death but enhanced cytokine production in a RIPK1- and RIPK3 kinase activity-dependent manner. Lastly, we provide evidence that ZBP1 signaling contributes to SARS-CoV-2-induced cytokine production. Taken together, we describe a ZBP1-RIPK3-RIPK1-mediated inflammatory signaling pathway relayed by the scaffolding role of RIPKs and regulated by caspases, which may induce inflammation when ZBP1 is activated below the threshold needed to trigger a cell death response.

AB - ZBP1 is an interferon-induced cytosolic nucleic acid sensor that facilitates antiviral responses via RIPK3. Although ZBP1-mediated programmed cell death is widely described, whether and how it promotes inflammatory signaling is unclear. Here, we report a ZBP1-induced inflammatory signaling pathway mediated by K63- and M1-linked ubiquitin chains, which depends on RIPK1 and RIPK3 as scaffolds independently of cell death. In human HT29 cells, ZBP1 associated with RIPK1 and RIPK3 as well as ubiquitin ligases cIAP1 and LUBAC. ZBP1-induced K63- and M1-linked ubiquitination of RIPK1 and ZBP1 to promote TAK1- and IKK-mediated inflammatory signaling and cytokine production. Inhibition of caspase activity suppressed ZBP1-induced cell death but enhanced cytokine production in a RIPK1- and RIPK3 kinase activity-dependent manner. Lastly, we provide evidence that ZBP1 signaling contributes to SARS-CoV-2-induced cytokine production. Taken together, we describe a ZBP1-RIPK3-RIPK1-mediated inflammatory signaling pathway relayed by the scaffolding role of RIPKs and regulated by caspases, which may induce inflammation when ZBP1 is activated below the threshold needed to trigger a cell death response.

KW - inflammatory signaling

KW - RIPK1

KW - RIPK3

KW - SARS-CoV-2

KW - ZBP1

U2 - 10.15252/embr.202255839

DO - 10.15252/embr.202255839

M3 - Journal article

C2 - 36268590

AN - SCOPUS:85140124395

VL - 2022

JO - E M B O Reports

JF - E M B O Reports

SN - 1469-221X

IS - 23

M1 - e55839

ER -

ID: 323969359