{"@context":{"@vocab":"https://cir.nii.ac.jp/schema/1.0/","rdfs":"http://www.w3.org/2000/01/rdf-schema#","dc":"http://purl.org/dc/elements/1.1/","dcterms":"http://purl.org/dc/terms/","foaf":"http://xmlns.com/foaf/0.1/","prism":"http://prismstandard.org/namespaces/basic/2.0/","cinii":"http://ci.nii.ac.jp/ns/1.0/","datacite":"https://schema.datacite.org/meta/kernel-4/","ndl":"http://ndl.go.jp/dcndl/terms/","jpcoar":"https://github.com/JPCOAR/schema/blob/master/2.0/"},"@id":"https://cir.nii.ac.jp/crid/1361699994182695680.json","@type":"Article","productIdentifier":[{"identifier":{"@type":"DOI","@value":"10.1073/pnas.1400419111"}},{"identifier":{"@type":"URI","@value":"https://pnas.org/doi/pdf/10.1073/pnas.1400419111"}}],"dc:title":[{"@value":"Blocking CD40-TRAF6 signaling is a therapeutic target in obesity-associated insulin resistance"}],"description":[{"type":"abstract","notation":[{"@value":"<jats:title>Significance</jats:title>\n          <jats:p>Inflammation is a critical contributor to the pathogenesis of metabolic disorders associated with obesity. A group of molecules crucial in regulating the immune system are costimulatory molecules, including CD40. Our current study shows that CD40 acts as a double-edged sword in the metabolic syndrome through the initiation of differential signaling cascades. The CD40-TNF receptor-associated factor (TRAF) 2/3/5 signaling pathway protects against metabolic dysfunction and inflammation associated with obesity; conversely, the CD40-TRAF6 pathway contributes to the detrimental consequences of obesity. In the present study, we therefore designed, validated, and used a small-molecule inhibitor that blocks CD40-TRAF6 interactions. The improvement of insulin resistance by this specific CD40-TRAF6 inhibitor could represent a therapeutic breakthrough in the field of immunometabolism.</jats:p>"}]}],"creator":[{"@id":"https://cir.nii.ac.jp/crid/1380013199372081667","@type":"Researcher","foaf:name":[{"@value":"Antonios Chatzigeorgiou"}],"jpcoar:affiliationName":[{"@value":"Department of Clinical Pathobiochemistry, Technische Universität Dresden, 01307 Dresden, Germany;"},{"@value":"Department of Medicine, Technische Universität Dresden, 01307 Dresden, Germany;"},{"@value":"Paul-Langerhans Institute Dresden, German Center for Diabetes Research, 01307 Dresden, Germany;"}]},{"@id":"https://cir.nii.ac.jp/crid/1380013199372081543","@type":"Researcher","foaf:name":[{"@value":"Tom Seijkens"}],"jpcoar:affiliationName":[{"@value":"Department of Medical Biochemistry, Subdivision of Experimental Vascular Biology, Academic Medical Center, University of Amsterdam, 1105 AZ, Amsterdam, The Netherlands;"}]},{"@id":"https://cir.nii.ac.jp/crid/1380013199372081676","@type":"Researcher","foaf:name":[{"@value":"Barbara Zarzycka"}],"jpcoar:affiliationName":[{"@value":"Department of Biochemistry, University of Maastricht, 6229 ER, Maastricht, The Netherlands;"}]},{"@id":"https://cir.nii.ac.jp/crid/1380013199372081542","@type":"Researcher","foaf:name":[{"@value":"David Engel"}],"jpcoar:affiliationName":[{"@value":"Department of Pathology, University of Maastricht, 6229 ER, Maastricht, The Netherlands;"}]},{"@id":"https://cir.nii.ac.jp/crid/1380013199372081673","@type":"Researcher","foaf:name":[{"@value":"Marjorie Poggi"}],"jpcoar:affiliationName":[{"@value":"Department of Pathology, University of Maastricht, 6229 ER, Maastricht, The Netherlands;"},{"@value":"Institut National de la Santé et de la Recherche Médicale, Unité Mixte de Recherche 1062, and Faculté de Médecine, Aix-Marseille Université, F-13385 Marseille, France;"}]},{"@id":"https://cir.nii.ac.jp/crid/1380013199372081671","@type":"Researcher","foaf:name":[{"@value":"Susan van den Berg"}],"jpcoar:affiliationName":[{"@value":"Department of Medical Biochemistry, Subdivision of Experimental Vascular Biology, Academic Medical Center, University of Amsterdam, 1105 AZ, Amsterdam, The Netherlands;"}]},{"@id":"https://cir.nii.ac.jp/crid/1380013199372081558","@type":"Researcher","foaf:name":[{"@value":"Sjoerd van den Berg"}],"jpcoar:affiliationName":[{"@value":"Department of Human Genetics, Leiden University Medical Center, 2333 ZA, Leiden, The Netherlands;"}]},{"@id":"https://cir.nii.ac.jp/crid/1380013199372081539","@type":"Researcher","foaf:name":[{"@value":"Oliver Soehnlein"}],"jpcoar:affiliationName":[{"@value":"Department of Pathology, Academic Medical Center, University of Amsterdam, 1105 AZ, Amsterdam, The Netherlands;"},{"@value":"Institute for Cardiovascular Prevention, Ludwig Maximilians University, 80336 Munich, Germany;"}]},{"@id":"https://cir.nii.ac.jp/crid/1380013199372081675","@type":"Researcher","foaf:name":[{"@value":"Holger Winkels"}],"jpcoar:affiliationName":[{"@value":"Department of Medical Biochemistry, Subdivision of Experimental Vascular Biology, Academic Medical Center, University of Amsterdam, 1105 AZ, Amsterdam, The Netherlands;"},{"@value":"Institute for Cardiovascular Prevention, Ludwig Maximilians University, 80336 Munich, Germany;"}]},{"@id":"https://cir.nii.ac.jp/crid/1380013199372081536","@type":"Researcher","foaf:name":[{"@value":"Linda Beckers"}],"jpcoar:affiliationName":[{"@value":"Department of Medical Biochemistry, Subdivision of Experimental Vascular Biology, Academic Medical Center, University of Amsterdam, 1105 AZ, Amsterdam, The Netherlands;"}]},{"@id":"https://cir.nii.ac.jp/crid/1380013199372081672","@type":"Researcher","foaf:name":[{"@value":"Dirk Lievens"}],"jpcoar:affiliationName":[{"@value":"Department of Medical Biochemistry, Subdivision of Experimental Vascular Biology, Academic Medical Center, University of Amsterdam, 1105 AZ, Amsterdam, The Netherlands;"},{"@value":"Institute for Cardiovascular Prevention, Ludwig Maximilians University, 80336 Munich, Germany;"}]},{"@id":"https://cir.nii.ac.jp/crid/1380013199372081545","@type":"Researcher","foaf:name":[{"@value":"Ann Driessen"}],"jpcoar:affiliationName":[{"@value":"Department of Pathology, University of Antwerp, 2650 Antwerp, Belgium;"}]},{"@id":"https://cir.nii.ac.jp/crid/1380013199372081547","@type":"Researcher","foaf:name":[{"@value":"Pascal Kusters"}],"jpcoar:affiliationName":[{"@value":"Department of Medical Biochemistry, Subdivision of Experimental Vascular Biology, Academic Medical Center, University of Amsterdam, 1105 AZ, Amsterdam, The Netherlands;"}]},{"@id":"https://cir.nii.ac.jp/crid/1380013199372081546","@type":"Researcher","foaf:name":[{"@value":"Erik Biessen"}],"jpcoar:affiliationName":[{"@value":"Department of Pathology, University of Maastricht, 6229 ER, Maastricht, The Netherlands;"}]},{"@id":"https://cir.nii.ac.jp/crid/1380013199372081555","@type":"Researcher","foaf:name":[{"@value":"Ruben Garcia-Martin"}],"jpcoar:affiliationName":[{"@value":"Department of Clinical Pathobiochemistry, Technische Universität Dresden, 01307 Dresden, Germany;"}]},{"@id":"https://cir.nii.ac.jp/crid/1380013199372081666","@type":"Researcher","foaf:name":[{"@value":"Anne Klotzsche-von Ameln"}],"jpcoar:affiliationName":[{"@value":"Department of Clinical Pathobiochemistry, Technische Universität Dresden, 01307 Dresden, Germany;"}]},{"@id":"https://cir.nii.ac.jp/crid/1380013199372081550","@type":"Researcher","foaf:name":[{"@value":"Marion Gijbels"}],"jpcoar:affiliationName":[{"@value":"Department of Medical Biochemistry, Subdivision of Experimental Vascular Biology, Academic Medical Center, University of Amsterdam, 1105 AZ, Amsterdam, The Netherlands;"},{"@value":"Department of Pathology, University of Maastricht, 6229 ER, Maastricht, The Netherlands;"},{"@value":"Cardiovascular Research Institute Maastricht, Maastricht University, 6229 ER, Maastricht, The Netherlands;"}]},{"@id":"https://cir.nii.ac.jp/crid/1380013199372081548","@type":"Researcher","foaf:name":[{"@value":"Randolph Noelle"}],"jpcoar:affiliationName":[{"@value":"Department of Microbiology and Immunology, Geisel School of Medicine at Dartmouth, Lebanon, NH 03766;"},{"@value":"Medical Research Council Centre of Transplantation, Guy’s Hospital, King’s College London, London SE1 9RT, United Kingdom;"}]},{"@id":"https://cir.nii.ac.jp/crid/1380013199372081552","@type":"Researcher","foaf:name":[{"@value":"Louis Boon"}],"jpcoar:affiliationName":[{"@value":"Bioceros BV, 3584 CM, Utrecht, The Netherlands;"}]},{"@id":"https://cir.nii.ac.jp/crid/1380013199372081553","@type":"Researcher","foaf:name":[{"@value":"Tilman Hackeng"}],"jpcoar:affiliationName":[{"@value":"Department of Biochemistry, University of Maastricht, 6229 ER, Maastricht, The Netherlands;"}]},{"@id":"https://cir.nii.ac.jp/crid/1380013199372081674","@type":"Researcher","foaf:name":[{"@value":"Klaus-Martin Schulte"}],"jpcoar:affiliationName":[{"@value":"Department of Endocrine Surgery, King's College Hospital, Denmark Hill, London SE5 9RS, United Kingdom;"}]},{"@id":"https://cir.nii.ac.jp/crid/1380013199372081664","@type":"Researcher","foaf:name":[{"@value":"Aimin Xu"}],"jpcoar:affiliationName":[{"@value":"Department of Medicine, University of Hong Kong, Hong Kong, China;"}]},{"@id":"https://cir.nii.ac.jp/crid/1380013199372081665","@type":"Researcher","foaf:name":[{"@value":"Gert Vriend"}],"jpcoar:affiliationName":[{"@value":"Centre for Molecular and Biomolecular Informatics, Radboud University Medical Center, 6295 EN, Nijmegen, The Netherlands;"}]},{"@id":"https://cir.nii.ac.jp/crid/1380013199372081670","@type":"Researcher","foaf:name":[{"@value":"Sander Nabuurs"}],"jpcoar:affiliationName":[{"@value":"Centre for Molecular and Biomolecular Informatics, Radboud University Medical Center, 6295 EN, Nijmegen, The Netherlands;"},{"@value":"Lead Pharma Medicine, 6525 EN, Nijmegen, The Netherlands;"}]},{"@id":"https://cir.nii.ac.jp/crid/1380013199372081669","@type":"Researcher","foaf:name":[{"@value":"Kyoung-Jin Chung"}],"jpcoar:affiliationName":[{"@value":"Department of Clinical Pathobiochemistry, Technische Universität Dresden, 01307 Dresden, Germany;"}]},{"@id":"https://cir.nii.ac.jp/crid/1380013199372081541","@type":"Researcher","foaf:name":[{"@value":"Ko Willems van Dijk"}],"jpcoar:affiliationName":[{"@value":"Department of Human Genetics, Leiden University Medical Center, 2333 ZA, Leiden, The Netherlands;"},{"@value":"Einthoven Laboratory for Experimental Vascular Medicine, Leiden University Medical Center, 2333 ZA, Leiden, The Netherlands;"}]},{"@id":"https://cir.nii.ac.jp/crid/1380013199372081556","@type":"Researcher","foaf:name":[{"@value":"Patrick C. N. Rensen"}],"jpcoar:affiliationName":[{"@value":"Einthoven Laboratory for Experimental Vascular Medicine, Leiden University Medical Center, 2333 ZA, Leiden, The Netherlands;"},{"@value":"Department of Endocrinology, Leiden University Medical Center, 2333 ZA, Leiden, The Netherlands;"}]},{"@id":"https://cir.nii.ac.jp/crid/1380013199372081537","@type":"Researcher","foaf:name":[{"@value":"Norbert Gerdes"}],"jpcoar:affiliationName":[{"@value":"Department of Medical Biochemistry, Subdivision of Experimental Vascular Biology, Academic Medical Center, University of Amsterdam, 1105 AZ, Amsterdam, The Netherlands;"},{"@value":"Institute for Cardiovascular Prevention, Ludwig Maximilians University, 80336 Munich, Germany;"}]},{"@id":"https://cir.nii.ac.jp/crid/1380013199372081554","@type":"Researcher","foaf:name":[{"@value":"Menno de Winther"}],"jpcoar:affiliationName":[{"@value":"Department of Medical Biochemistry, Subdivision of Experimental Vascular Biology, Academic Medical Center, University of Amsterdam, 1105 AZ, Amsterdam, The Netherlands;"}]},{"@id":"https://cir.nii.ac.jp/crid/1380013199372081540","@type":"Researcher","foaf:name":[{"@value":"Norman L. Block"}],"jpcoar:affiliationName":[{"@value":"Divisions of Endocrinology and Hematology–Oncology, Departments of Pathology and Medicine, University of Miami Miller School of Medicine, Miami, FL 33136;"},{"@value":"Veterans Affairs Medical Center, Miami, FL 33125;"}]},{"@id":"https://cir.nii.ac.jp/crid/1380013199372081551","@type":"Researcher","foaf:name":[{"@value":"Andrew V. Schally"}],"jpcoar:affiliationName":[{"@value":"Divisions of Endocrinology and Hematology–Oncology, Departments of Pathology and Medicine, University of Miami Miller School of Medicine, Miami, FL 33136;"},{"@value":"Veterans Affairs Medical Center, Miami, FL 33125;"}]},{"@id":"https://cir.nii.ac.jp/crid/1380013199372081549","@type":"Researcher","foaf:name":[{"@value":"Christian Weber"}],"jpcoar:affiliationName":[{"@value":"Department of Biochemistry, University of Maastricht, 6229 ER, Maastricht, The Netherlands;"},{"@value":"Institute for Cardiovascular Prevention, Ludwig Maximilians University, 80336 Munich, Germany;"},{"@value":"German Centre for Cardiovascular Research, Munich, 80336, Germany;"}]},{"@id":"https://cir.nii.ac.jp/crid/1380013199372081544","@type":"Researcher","foaf:name":[{"@value":"Stefan R. Bornstein"}],"jpcoar:affiliationName":[{"@value":"Department of Medicine, Technische Universität Dresden, 01307 Dresden, Germany;"},{"@value":"Diabetes and Nutritional Sciences Division, King's College London, Denmark Hill, London SE5 9NU, United Kingdom; and"}]},{"@id":"https://cir.nii.ac.jp/crid/1380013199372081538","@type":"Researcher","foaf:name":[{"@value":"Gerry Nicolaes"}],"jpcoar:affiliationName":[{"@value":"Department of Biochemistry, University of Maastricht, 6229 ER, Maastricht, The Netherlands;"}]},{"@id":"https://cir.nii.ac.jp/crid/1380013199372081557","@type":"Researcher","foaf:name":[{"@value":"Triantafyllos Chavakis"}],"jpcoar:affiliationName":[{"@value":"Department of Clinical Pathobiochemistry, Technische Universität Dresden, 01307 Dresden, Germany;"},{"@value":"Department of Medicine, Technische Universität Dresden, 01307 Dresden, Germany;"},{"@value":"Paul-Langerhans Institute Dresden, German Center for Diabetes Research, 01307 Dresden, Germany;"},{"@value":"Institute for Clinical Chemistry and Laboratory Medicine, Technische Universität Dresden, 01307 Dresden, Germany"}]},{"@id":"https://cir.nii.ac.jp/crid/1380013199372081668","@type":"Researcher","foaf:name":[{"@value":"Esther Lutgens"}],"jpcoar:affiliationName":[{"@value":"Department of Medical Biochemistry, Subdivision of Experimental Vascular Biology, Academic Medical Center, University of Amsterdam, 1105 AZ, Amsterdam, The Netherlands;"},{"@value":"Institute for Cardiovascular Prevention, Ludwig Maximilians University, 80336 Munich, Germany;"}]}],"publication":{"publicationIdentifier":[{"@type":"PISSN","@value":"00278424"},{"@type":"EISSN","@value":"10916490"}],"prism:publicationName":[{"@value":"Proceedings of the National Academy of Sciences"}],"dc:publisher":[{"@value":"Proceedings of the National Academy of Sciences"}],"prism:publicationDate":"2014-02-03","prism:volume":"111","prism:number":"7","prism:startingPage":"2686","prism:endingPage":"2691"},"reviewed":"false","url":[{"@id":"https://pnas.org/doi/pdf/10.1073/pnas.1400419111"}],"createdAt":"2014-02-04","modifiedAt":"2022-04-13","relatedProduct":[{"@id":"https://cir.nii.ac.jp/crid/1360285709150197376","@type":"Article","resourceType":"学術雑誌論文(journal article)","relationType":["isReferencedBy"],"jpcoar:relatedTitle":[{"@value":"<i>In vitro</i> and <i>in vivo</i> cancer cell apoptosis triggered by competitive binding of <i>Cinchona</i> alkaloids to the RING domain of TRAF6"}]}],"dataSourceIdentifier":[{"@type":"CROSSREF","@value":"10.1073/pnas.1400419111"},{"@type":"CROSSREF","@value":"10.1080/09168451.2018.1559030_references_DOI_9WOSDFPnLCCvtVVCedJsLgDkpWt"}]}