Viral MLKL Homologs Subvert Necroptotic Cell Death by Sequestering Cellular RIPK3.

Animals Cell Death Humans Immunity, Innate Mice Necrosis Protein Kinases / metabolism Receptor-Interacting Protein Serine-Threonine Kinases / metabolism
MLKL RIPK3 innate immunity necroptosis poxvirus programmed necrosis pseudokinase

Journal

Cell reports
ISSN: 2211-1247
Titre abrégé: Cell Rep
Pays: United States
ID NLM: 101573691

Informations de publication

Date de publication:
24 09 2019
Historique:
received: 02 11 2018
revised: 04 07 2019
accepted: 16 08 2019
entrez: 26 9 2019
pubmed: 26 9 2019
medline: 21 10 2020
Statut: ppublish

Résumé

Necroptotic cell death has been implicated in many human pathologies and is thought to have evolved as an innate immunity mechanism. The pathway relies on two key effectors: the kinase receptor-interacting protein kinase 3 (RIPK3) and the terminal effector, the pseudokinase mixed-lineage kinase-domain-like (MLKL). We identify proteins with high sequence similarity to the pseudokinase domain of MLKL in poxvirus genomes. Expression of these proteins from the BeAn 58058 and Cotia poxviruses, but not swinepox, in human and mouse cells blocks cellular MLKL activation and necroptotic cell death. We show that viral MLKL-like proteins function as dominant-negative mimics of host MLKL, which inhibit necroptosis by sequestering RIPK3 via its kinase domain to thwart MLKL engagement and phosphorylation. These data support an ancestral role for necroptosis in defense against pathogens. Furthermore, mimicry of a cellular pseudokinase by a pathogen adds to the growing repertoire of functions performed by pseudokinases in signal transduction.

Identifiants

DOI: 10.1016/j.celrep.2019.08.055 PMID: 31553902
pubmed: 31553902
pii: S2211-1247(19)31103-9
doi: 10.1016/j.celrep.2019.08.055
pii:
doi:

Substances chimiques

MLKL protein, human EC 2.7.-
Protein Kinases EC 2.7.-
RIPK3 protein, human EC 2.7.11.1
Receptor-Interacting Protein Serine-Threonine Kinases EC 2.7.11.1

Types de publication

Journal Article Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Pagination

3309-3319.e5

Informations de copyright

Copyright © 2019 The Author(s). Published by Elsevier Inc. All rights reserved.

Auteurs

Emma J Petrie (EJ)

The Walter and Eliza Hall Institute of Medical Research, Parkville, VIC 3052, Australia; Department of Medical Biology, University of Melbourne, Parkville, VIC 3052, Australia. Electronic address: petrie.e@wehi.edu.au.

Jarrod J Sandow (JJ)

The Walter and Eliza Hall Institute of Medical Research, Parkville, VIC 3052, Australia; Department of Medical Biology, University of Melbourne, Parkville, VIC 3052, Australia.

Wil I L Lehmann (WIL)

The Walter and Eliza Hall Institute of Medical Research, Parkville, VIC 3052, Australia; Department of Medical Biology, University of Melbourne, Parkville, VIC 3052, Australia.

Lung-Yu Liang (LY)

The Walter and Eliza Hall Institute of Medical Research, Parkville, VIC 3052, Australia; Department of Medical Biology, University of Melbourne, Parkville, VIC 3052, Australia.

Diane Coursier (D)

The Walter and Eliza Hall Institute of Medical Research, Parkville, VIC 3052, Australia.

Samuel N Young (SN)

The Walter and Eliza Hall Institute of Medical Research, Parkville, VIC 3052, Australia.

Wilhelmus J A Kersten (WJA)

The Walter and Eliza Hall Institute of Medical Research, Parkville, VIC 3052, Australia.

Cheree Fitzgibbon (C)

The Walter and Eliza Hall Institute of Medical Research, Parkville, VIC 3052, Australia.

André L Samson (AL)

The Walter and Eliza Hall Institute of Medical Research, Parkville, VIC 3052, Australia; Department of Medical Biology, University of Melbourne, Parkville, VIC 3052, Australia.

Annette V Jacobsen (AV)

The Walter and Eliza Hall Institute of Medical Research, Parkville, VIC 3052, Australia; Department of Medical Biology, University of Melbourne, Parkville, VIC 3052, Australia.

Kym N Lowes (KN)

The Walter and Eliza Hall Institute of Medical Research, Parkville, VIC 3052, Australia; Department of Medical Biology, University of Melbourne, Parkville, VIC 3052, Australia.

Amanda E Au (AE)

The Walter and Eliza Hall Institute of Medical Research, Parkville, VIC 3052, Australia; Department of Medical Biology, University of Melbourne, Parkville, VIC 3052, Australia.

Hélène Jousset Sabroux (H)

The Walter and Eliza Hall Institute of Medical Research, Parkville, VIC 3052, Australia; Department of Medical Biology, University of Melbourne, Parkville, VIC 3052, Australia.

Najoua Lalaoui (N)

The Walter and Eliza Hall Institute of Medical Research, Parkville, VIC 3052, Australia; Department of Medical Biology, University of Melbourne, Parkville, VIC 3052, Australia.

Andrew I Webb (AI)

The Walter and Eliza Hall Institute of Medical Research, Parkville, VIC 3052, Australia; Department of Medical Biology, University of Melbourne, Parkville, VIC 3052, Australia.

Guillaume Lessene (G)

The Walter and Eliza Hall Institute of Medical Research, Parkville, VIC 3052, Australia; Department of Medical Biology, University of Melbourne, Parkville, VIC 3052, Australia; Department of Pharmacology and Therapeutics, University of Melbourne, Parkville, VIC 3052, Australia.

Gerard Manning (G)

Department of Bioinformatics and Computational Biology, Genentech, Inc., South San Francisco, CA 94080, USA.

Isabelle S Lucet (IS)

The Walter and Eliza Hall Institute of Medical Research, Parkville, VIC 3052, Australia; Department of Medical Biology, University of Melbourne, Parkville, VIC 3052, Australia.

James M Murphy (JM)

The Walter and Eliza Hall Institute of Medical Research, Parkville, VIC 3052, Australia; Department of Medical Biology, University of Melbourne, Parkville, VIC 3052, Australia. Electronic address: jamesm@wehi.edu.au.

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Classifications MeSH

questionsmedicales.fr › Eucaryotes › Animaux › Viral MLKL Homologs Subvert Necroptotic Cell...
questionsmedicales.fr › Phénomènes physiologiques cellulaires › Mort cellulaire › Viral MLKL Homologs Subvert Necroptotic Cell...
questionsmedicales.fr › Eucaryotes › Animaux › Chordés › Vertébrés › Mammifères › Eutheria › Primates › Haplorhini › Catarrhini › Hominidae › Humains › Viral MLKL Homologs Subvert Necroptotic Cell...
questionsmedicales.fr › Phénomènes du système immunitaire › Immunité › Immunité innée › Viral MLKL Homologs Subvert Necroptotic Cell...
questionsmedicales.fr › Eucaryotes › Animaux › Chordés › Vertébrés › Mammifères › Eutheria › Rodentia › Muridae › Murinae › Souris › Viral MLKL Homologs Subvert Necroptotic Cell...
questionsmedicales.fr › États, signes et symptômes pathologiques › Processus pathologiques › Nécrose › Viral MLKL Homologs Subvert Necroptotic Cell...
questionsmedicales.fr › Enzymes et coenzymes › Enzymes › Transferases › Phosphotransferases › Phosphotransferases (Alcohol Group Acceptor) › Protein kinases › Viral MLKL Homologs Subvert Necroptotic Cell...
questionsmedicales.fr › Acides aminés, peptides et protéines › Protéines › Protéines et peptides de signalisation intracellulaire › Protein-Serine-Threonine Kinases › Receptor-Interacting Protein Serine-Threonine Kinases › Viral MLKL Homologs Subvert Necroptotic Cell...