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Serine 25 phosphorylation inhibits RIPK1 kinase-dependent cell death in models of infection and inflammation

Standard

Serine 25 phosphorylation inhibits RIPK1 kinase-dependent cell death in models of infection and inflammation. / Dondelinger, Yves; Delanghe, Tom; Priem, Dario; Wynosky-Dolfi, Meghan A; Sorobetea, Daniel; Rojas-Rivera, Diego; Giansanti, Piero; Roelandt, Ria; Gropengiesser, Julia; Ruckdeschel, Klaus; Savvides, Savvas N; Heck, Albert J R; Vandenabeele, Peter; Brodsky, Igor E; Bertrand, Mathieu J M.

in: NAT COMMUN, Jahrgang 10, Nr. 1, 15.04.2019, S. 1729.

Publikationen: SCORING: Beitrag in Fachzeitschrift/Zeitung › SCORING: Zeitschriftenaufsatz › Forschung › Begutachtung

Harvard

Dondelinger, Y, Delanghe, T, Priem, D, Wynosky-Dolfi, MA, Sorobetea, D, Rojas-Rivera, D, Giansanti, P, Roelandt, R, Gropengiesser, J, Ruckdeschel, K, Savvides, SN, Heck, AJR, Vandenabeele, P, Brodsky, IE & Bertrand, MJM 2019, 'Serine 25 phosphorylation inhibits RIPK1 kinase-dependent cell death in models of infection and inflammation', NAT COMMUN, Jg. 10, Nr. 1, S. 1729. https://doi.org/10.1038/s41467-019-09690-0

APA

Dondelinger, Y., Delanghe, T., Priem, D., Wynosky-Dolfi, M. A., Sorobetea, D., Rojas-Rivera, D., Giansanti, P., Roelandt, R., Gropengiesser, J., Ruckdeschel, K., Savvides, S. N., Heck, A. J. R., Vandenabeele, P., Brodsky, I. E., & Bertrand, M. J. M. (2019). Serine 25 phosphorylation inhibits RIPK1 kinase-dependent cell death in models of infection and inflammation. NAT COMMUN, 10(1), 1729. https://doi.org/10.1038/s41467-019-09690-0

Vancouver

Dondelinger Y, Delanghe T, Priem D, Wynosky-Dolfi MA, Sorobetea D, Rojas-Rivera D et al. Serine 25 phosphorylation inhibits RIPK1 kinase-dependent cell death in models of infection and inflammation. NAT COMMUN. 2019 Apr 15;10(1):1729. https://doi.org/10.1038/s41467-019-09690-0

Bibtex

@article{8848b9330a504d6c9f6fafca04604283,
title = "Serine 25 phosphorylation inhibits RIPK1 kinase-dependent cell death in models of infection and inflammation",
abstract = "RIPK1 regulates cell death and inflammation through kinase-dependent and -independent mechanisms. As a scaffold, RIPK1 inhibits caspase-8-dependent apoptosis and RIPK3/MLKL-dependent necroptosis. As a kinase, RIPK1 paradoxically induces these cell death modalities. The molecular switch between RIPK1 pro-survival and pro-death functions remains poorly understood. We identify phosphorylation of RIPK1 on Ser25 by IKKs as a key mechanism directly inhibiting RIPK1 kinase activity and preventing TNF-mediated RIPK1-dependent cell death. Mimicking Ser25 phosphorylation (S > D mutation) protects cells and mice from the cytotoxic effect of TNF in conditions of IKK inhibition. In line with their roles in IKK activation, TNF-induced Ser25 phosphorylation of RIPK1 is defective in TAK1- or SHARPIN-deficient cells and restoring phosphorylation protects these cells from TNF-induced death. Importantly, mimicking Ser25 phosphorylation compromises the in vivo cell death-dependent immune control of Yersinia infection, a physiological model of TAK1/IKK inhibition, and rescues the cell death-induced multi-organ inflammatory phenotype of the SHARPIN-deficient mice.",
keywords = "Animals, Apoptosis, Caspase 8/genetics, Cell Line, I-kappa B Kinase/metabolism, Immunity/physiology, Mice, Models, Immunological, Phosphorylation, Receptor-Interacting Protein Serine-Threonine Kinases/chemistry, Serine/chemistry, Yersinia, Yersinia Infections/immunology",
author = "Yves Dondelinger and Tom Delanghe and Dario Priem and Wynosky-Dolfi, {Meghan A} and Daniel Sorobetea and Diego Rojas-Rivera and Piero Giansanti and Ria Roelandt and Julia Gropengiesser and Klaus Ruckdeschel and Savvides, {Savvas N} and Heck, {Albert J R} and Peter Vandenabeele and Brodsky, {Igor E} and Bertrand, {Mathieu J M}",
year = "2019",
month = apr,
day = "15",
doi = "10.1038/s41467-019-09690-0",
language = "English",
volume = "10",
pages = "1729",
journal = "NAT COMMUN",
issn = "2041-1723",
publisher = "NATURE PUBLISHING GROUP",
number = "1",

}

RIS

TY - JOUR

T1 - Serine 25 phosphorylation inhibits RIPK1 kinase-dependent cell death in models of infection and inflammation

AU - Dondelinger, Yves

AU - Delanghe, Tom

AU - Priem, Dario

AU - Wynosky-Dolfi, Meghan A

AU - Sorobetea, Daniel

AU - Rojas-Rivera, Diego

AU - Giansanti, Piero

AU - Roelandt, Ria

AU - Gropengiesser, Julia

AU - Ruckdeschel, Klaus

AU - Savvides, Savvas N

AU - Heck, Albert J R

AU - Vandenabeele, Peter

AU - Brodsky, Igor E

AU - Bertrand, Mathieu J M

PY - 2019/4/15

Y1 - 2019/4/15

N2 - RIPK1 regulates cell death and inflammation through kinase-dependent and -independent mechanisms. As a scaffold, RIPK1 inhibits caspase-8-dependent apoptosis and RIPK3/MLKL-dependent necroptosis. As a kinase, RIPK1 paradoxically induces these cell death modalities. The molecular switch between RIPK1 pro-survival and pro-death functions remains poorly understood. We identify phosphorylation of RIPK1 on Ser25 by IKKs as a key mechanism directly inhibiting RIPK1 kinase activity and preventing TNF-mediated RIPK1-dependent cell death. Mimicking Ser25 phosphorylation (S > D mutation) protects cells and mice from the cytotoxic effect of TNF in conditions of IKK inhibition. In line with their roles in IKK activation, TNF-induced Ser25 phosphorylation of RIPK1 is defective in TAK1- or SHARPIN-deficient cells and restoring phosphorylation protects these cells from TNF-induced death. Importantly, mimicking Ser25 phosphorylation compromises the in vivo cell death-dependent immune control of Yersinia infection, a physiological model of TAK1/IKK inhibition, and rescues the cell death-induced multi-organ inflammatory phenotype of the SHARPIN-deficient mice.

AB - RIPK1 regulates cell death and inflammation through kinase-dependent and -independent mechanisms. As a scaffold, RIPK1 inhibits caspase-8-dependent apoptosis and RIPK3/MLKL-dependent necroptosis. As a kinase, RIPK1 paradoxically induces these cell death modalities. The molecular switch between RIPK1 pro-survival and pro-death functions remains poorly understood. We identify phosphorylation of RIPK1 on Ser25 by IKKs as a key mechanism directly inhibiting RIPK1 kinase activity and preventing TNF-mediated RIPK1-dependent cell death. Mimicking Ser25 phosphorylation (S > D mutation) protects cells and mice from the cytotoxic effect of TNF in conditions of IKK inhibition. In line with their roles in IKK activation, TNF-induced Ser25 phosphorylation of RIPK1 is defective in TAK1- or SHARPIN-deficient cells and restoring phosphorylation protects these cells from TNF-induced death. Importantly, mimicking Ser25 phosphorylation compromises the in vivo cell death-dependent immune control of Yersinia infection, a physiological model of TAK1/IKK inhibition, and rescues the cell death-induced multi-organ inflammatory phenotype of the SHARPIN-deficient mice.

KW - Animals

KW - Apoptosis

KW - Caspase 8/genetics

KW - Cell Line

KW - I-kappa B Kinase/metabolism

KW - Immunity/physiology

KW - Mice

KW - Models, Immunological

KW - Phosphorylation

KW - Receptor-Interacting Protein Serine-Threonine Kinases/chemistry

KW - Serine/chemistry

KW - Yersinia

KW - Yersinia Infections/immunology

U2 - 10.1038/s41467-019-09690-0

DO - 10.1038/s41467-019-09690-0

M3 - SCORING: Journal article

C2 - 30988283

VL - 10

SP - 1729

JO - NAT COMMUN

JF - NAT COMMUN

SN - 2041-1723

IS - 1

ER -