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Caspase-11 cleaves gasdermin D for non-canonical inflammasome signalling.
Kayagaki, Nobuhiko; Stowe, Irma B; Lee, Bettina L; O'Rourke, Karen; Anderson, Keith; Warming, Søren; Cuellar, Trinna; Haley, Benjamin; Roose-Girma, Merone; Phung, Qui T; Liu, Peter S; Lill, Jennie R; Li, Hong; Wu, Jiansheng; Kummerfeld, Sarah; Zhang, Juan; Lee, Wyne P; Snipas, Scott J; Salvesen, Guy S; Morris, Lucy X; Fitzgerald, Linda; Zhang, Yafei; Bertram, Edward M; Goodnow, Christopher C; Dixit, Vishva M.
Afiliación
  • Kayagaki N; Department of Physiological Chemistry, Genentech Inc., South San Francisco, California 94080, USA.
  • Stowe IB; Department of Physiological Chemistry, Genentech Inc., South San Francisco, California 94080, USA.
  • Lee BL; Department of Physiological Chemistry, Genentech Inc., South San Francisco, California 94080, USA.
  • O'Rourke K; Department of Physiological Chemistry, Genentech Inc., South San Francisco, California 94080, USA.
  • Anderson K; Department of Molecular Biology, Genentech Inc., South San Francisco, California 94080, USA.
  • Warming S; Department of Molecular Biology, Genentech Inc., South San Francisco, California 94080, USA.
  • Cuellar T; Department of Molecular Biology, Genentech Inc., South San Francisco, California 94080, USA.
  • Haley B; Department of Molecular Biology, Genentech Inc., South San Francisco, California 94080, USA.
  • Roose-Girma M; Department of Molecular Biology, Genentech Inc., South San Francisco, California 94080, USA.
  • Phung QT; Department of Protein Chemistry, Genentech Inc., South San Francisco, California 94080, USA.
  • Liu PS; Department of Protein Chemistry, Genentech Inc., South San Francisco, California 94080, USA.
  • Lill JR; Department of Protein Chemistry, Genentech Inc., South San Francisco, California 94080, USA.
  • Li H; Department of Protein Chemistry, Genentech Inc., South San Francisco, California 94080, USA.
  • Wu J; Department of Protein Chemistry, Genentech Inc., South San Francisco, California 94080, USA.
  • Kummerfeld S; Department of Bioinformatics, Genentech Inc., South San Francisco, California 94080, USA.
  • Zhang J; Department of Immunology, Genentech Inc., South San Francisco, California 94080, USA.
  • Lee WP; Department of Immunology, Genentech Inc., South San Francisco, California 94080, USA.
  • Snipas SJ; Program in Cell Death Signaling Networks, Sanford-Burnham-Prebys Medical Discovery Institute, La Jolla, California 92037, USA.
  • Salvesen GS; Program in Cell Death Signaling Networks, Sanford-Burnham-Prebys Medical Discovery Institute, La Jolla, California 92037, USA.
  • Morris LX; The Australian Phenomics Facility, The John Curtin School of Medical Research, The Australian National University, Canberra, Australian Capital Territory 2601, Australia.
  • Fitzgerald L; The Australian Phenomics Facility, The John Curtin School of Medical Research, The Australian National University, Canberra, Australian Capital Territory 2601, Australia.
  • Zhang Y; The Australian Phenomics Facility, The John Curtin School of Medical Research, The Australian National University, Canberra, Australian Capital Territory 2601, Australia.
  • Bertram EM; The Australian Phenomics Facility, The John Curtin School of Medical Research, The Australian National University, Canberra, Australian Capital Territory 2601, Australia.
  • Goodnow CC; Department of Immunology and Infectious Diseases, The John Curtin School of Medical Research, The Australian National University, Canberra, Australian Capital Territory 2601, Australia.
  • Dixit VM; Department of Immunology and Infectious Diseases, The John Curtin School of Medical Research, The Australian National University, Canberra, Australian Capital Territory 2601, Australia.
Nature ; 526(7575): 666-71, 2015 Oct 29.
Article en En | MEDLINE | ID: mdl-26375259
Intracellular lipopolysaccharide from Gram-negative bacteria including Escherichia coli, Salmonella typhimurium, Shigella flexneri, and Burkholderia thailandensis activates mouse caspase-11, causing pyroptotic cell death, interleukin-1ß processing, and lethal septic shock. How caspase-11 executes these downstream signalling events is largely unknown. Here we show that gasdermin D is essential for caspase-11-dependent pyroptosis and interleukin-1ß maturation. A forward genetic screen with ethyl-N-nitrosourea-mutagenized mice links Gsdmd to the intracellular lipopolysaccharide response. Macrophages from Gsdmd(-/-) mice generated by gene targeting also exhibit defective pyroptosis and interleukin-1ß secretion induced by cytoplasmic lipopolysaccharide or Gram-negative bacteria. In addition, Gsdmd(-/-) mice are protected from a lethal dose of lipopolysaccharide. Mechanistically, caspase-11 cleaves gasdermin D, and the resulting amino-terminal fragment promotes both pyroptosis and NLRP3-dependent activation of caspase-1 in a cell-intrinsic manner. Our data identify gasdermin D as a critical target of caspase-11 and a key mediator of the host response against Gram-negative bacteria.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Transducción de Señal / Caspasas / Proteínas Reguladoras de la Apoptosis / Inflamasomas Tipo de estudio: Prognostic_studies Límite: Animals / Female / Humans / Male Idioma: En Revista: Nature Año: 2015 Tipo del documento: Article País de afiliación: Estados Unidos
Texto completo
Añadir a Mi BVS
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PubMed Links
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Transducción de Señal / Caspasas / Proteínas Reguladoras de la Apoptosis / Inflamasomas Tipo de estudio: Prognostic_studies Límite: Animals / Female / Humans / Male Idioma: En Revista: Nature Año: 2015 Tipo del documento: Article País de afiliación: Estados Unidos