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Ubiquitin Ligase TRIM62 Regulates CARD9-Mediated Anti-fungal Immunity and Intestinal Inflammation.
Cao, Zhifang; Conway, Kara L; Heath, Robert J; Rush, Jason S; Leshchiner, Elizaveta S; Ramirez-Ortiz, Zaida G; Nedelsky, Natalia B; Huang, Hailiang; Ng, Aylwin; Gardet, Agnès; Cheng, Shih-Chin; Shamji, Alykhan F; Rioux, John D; Wijmenga, Cisca; Netea, Mihai G; Means, Terry K; Daly, Mark J; Xavier, Ramnik J.
Afiliação
  • Cao Z; Gastrointestinal Unit and Center for the Study of Inflammatory Bowel Disease, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02114, USA; Center for Computational and Integrative Biology, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02114, USA.
  • Conway KL; Gastrointestinal Unit and Center for the Study of Inflammatory Bowel Disease, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02114, USA; Center for Computational and Integrative Biology, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02114, USA; Broad In
  • Heath RJ; Gastrointestinal Unit and Center for the Study of Inflammatory Bowel Disease, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02114, USA; Center for Computational and Integrative Biology, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02114, USA; Broad In
  • Rush JS; Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA.
  • Leshchiner ES; Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA.
  • Ramirez-Ortiz ZG; Center for Immunology and Inflammatory Diseases and Division of Rheumatology, Allergy, and Immunology, Massachusetts General Hospital and Harvard Medical School, Charlestown, MA 02129, USA.
  • Nedelsky NB; Gastrointestinal Unit and Center for the Study of Inflammatory Bowel Disease, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02114, USA; Center for Computational and Integrative Biology, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02114, USA.
  • Huang H; Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA; Analytic and Translational Genetics Unit, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02114, USA.
  • Ng A; Gastrointestinal Unit and Center for the Study of Inflammatory Bowel Disease, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02114, USA; Center for Computational and Integrative Biology, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02114, USA; Broad In
  • Gardet A; Gastrointestinal Unit and Center for the Study of Inflammatory Bowel Disease, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02114, USA; Center for Computational and Integrative Biology, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02114, USA.
  • Cheng SC; Department of Internal Medicine and Radboud Center for Infectious Diseases, Radboud University Nijmegen Medical Center, Nijmegen 6525 GA, the Netherlands.
  • Shamji AF; Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA.
  • Rioux JD; Research Center, Montreal Heart Institute and Université de Montréal, QC H1T 1C8, Canada.
  • Wijmenga C; Department of Genetics, University Medical Center Groningen, University of Groningen, Groningen T9700 RB, the Netherlands.
  • Netea MG; Department of Internal Medicine and Radboud Center for Infectious Diseases, Radboud University Nijmegen Medical Center, Nijmegen 6525 GA, the Netherlands.
  • Means TK; Center for Immunology and Inflammatory Diseases and Division of Rheumatology, Allergy, and Immunology, Massachusetts General Hospital and Harvard Medical School, Charlestown, MA 02129, USA.
  • Daly MJ; Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA; Analytic and Translational Genetics Unit, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02114, USA.
  • Xavier RJ; Gastrointestinal Unit and Center for the Study of Inflammatory Bowel Disease, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02114, USA; Center for Computational and Integrative Biology, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02114, USA; Broad In
Immunity ; 43(4): 715-26, 2015 Oct 20.
Article em En | MEDLINE | ID: mdl-26488816
CARD9 is a central component of anti-fungal innate immune signaling via C-type lectin receptors, and several immune-related disorders are associated with CARD9 alterations. Here, we used a rare CARD9 variant that confers protection against inflammatory bowel disease as an entry point to investigating CARD9 regulation. We showed that the protective variant of CARD9, which is C-terminally truncated, acted in a dominant-negative manner for CARD9-mediated cytokine production, indicating an important role for the C terminus in CARD9 signaling. We identified TRIM62 as a CARD9 binding partner and showed that TRIM62 facilitated K27-linked poly-ubiquitination of CARD9. We identified K125 as the ubiquitinated residue on CARD9 and demonstrated that this ubiquitination was essential for CARD9 activity. Furthermore, we showed that similar to Card9-deficient mice, Trim62-deficient mice had increased susceptibility to fungal infection. In this study, we utilized a rare protective allele to uncover a TRIM62-mediated mechanism for regulation of CARD9 activation.
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Receptores de Angiotensina / Receptores de Endotelina / Ubiquitina-Proteína Ligases / Proteínas Adaptadoras de Sinalização CARD / Candidíase Invasiva Tipo de estudo: Prognostic_studies Idioma: En Revista: Immunity Assunto da revista: ALERGIA E IMUNOLOGIA Ano de publicação: 2015 Tipo de documento: Article País de afiliação: Estados Unidos
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Receptores de Angiotensina / Receptores de Endotelina / Ubiquitina-Proteína Ligases / Proteínas Adaptadoras de Sinalização CARD / Candidíase Invasiva Tipo de estudo: Prognostic_studies Idioma: En Revista: Immunity Assunto da revista: ALERGIA E IMUNOLOGIA Ano de publicação: 2015 Tipo de documento: Article País de afiliação: Estados Unidos