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Viral MLKL Homologs Subvert Necroptotic Cell Death by Sequestering Cellular RIPK3.
Petrie, Emma J; Sandow, Jarrod J; Lehmann, Wil I L; Liang, Lung-Yu; Coursier, Diane; Young, Samuel N; Kersten, Wilhelmus J A; Fitzgibbon, Cheree; Samson, André L; Jacobsen, Annette V; Lowes, Kym N; Au, Amanda E; Jousset Sabroux, Hélène; Lalaoui, Najoua; Webb, Andrew I; Lessene, Guillaume; Manning, Gerard; Lucet, Isabelle S; Murphy, James M.
Afiliação
  • 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.
  • 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.
  • 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.
  • 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.
  • Coursier D; The Walter and Eliza Hall Institute of Medical Research, Parkville, VIC 3052, Australia.
  • Young SN; The Walter and Eliza Hall Institute of Medical Research, Parkville, VIC 3052, Australia.
  • Kersten WJA; The Walter and Eliza Hall Institute of Medical Research, Parkville, VIC 3052, Australia.
  • Fitzgibbon C; The Walter and Eliza Hall Institute of Medical Research, Parkville, VIC 3052, Australia.
  • 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.
  • 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.
  • 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.
  • 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.
  • 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.
  • 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.
  • 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.
  • 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.
  • Manning G; Department of Bioinformatics and Computational Biology, Genentech, Inc., South San Francisco, CA 94080, USA.
  • 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.
  • 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.
Cell Rep ; 28(13): 3309-3319.e5, 2019 09 24.
Article em En | MEDLINE | ID: mdl-31553902
ABSTRACT
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.
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Proteínas Quinases / Proteína Serina-Treonina Quinases de Interação com Receptores Limite: Animals / Humans Idioma: En Revista: Cell Rep Ano de publicação: 2019 Tipo de documento: Article
Texto completo
Imprimir
XML
PubMed Links
Buscar no Google

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Proteínas Quinases / Proteína Serina-Treonina Quinases de Interação com Receptores Limite: Animals / Humans Idioma: En Revista: Cell Rep Ano de publicação: 2019 Tipo de documento: Article