{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,4]],"date-time":"2026-10-04T18:30:13Z","timestamp":1791138613121,"version":"4.1.0"},"reference-count":33,"publisher":"American Association for the Advancement of Science (AAAS)","issue":"6065","license":[{"start":{"date-parts":[[2012,1,13]],"date-time":"2012-01-13T00:00:00Z","timestamp":1326412800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/www.sciencemag.org\/site\/feature\/contribinfo\/prep\/license.xhtml"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["GM64750"],"award-info":[{"award-number":["GM64750"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Science"],"published-print":{"date-parts":[[2012,1,13]]},"abstract":"<jats:title>TACE Trafficking<\/jats:title>\n                  <jats:p>\n                    The cytokine tumor necrosis factor (TNF) is a major driver of inflammation and contributes to the immune pathology seen in a variety of diseases, including inflammatory bowel disease, rheumatoid arthritis, and sepsis. Soluble TNF is produced by cleavage of its ectodomain by the ADAM family metalloprotease, TNF\u03b1-converting enzyme (TACE). However, the molecular regulation of TACE is not understood (see the Perspective by\n                    <jats:bold>\n                      <jats:related-article xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" ext-link-type=\"doi\" issue=\"6065\" page=\"179\" related-article-type=\"in-this-issue\" vol=\"335\" xlink:href=\"10.1126\/science.1216815\">Lichtenthaler<\/jats:related-article>\n                    <\/jats:bold>\n                    ).\n                    <jats:bold>\n                      Adrain\n                      <jats:italic>et al.<\/jats:italic>\n                    <\/jats:bold>\n                    (p.\n                    <jats:related-article xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" ext-link-type=\"doi\" page=\"225\" related-article-type=\"in-this-issue\" vol=\"335\" xlink:href=\"10.1126\/science.1214400\">225<\/jats:related-article>\n                    ) and\n                    <jats:bold>\n                      McIlwain\n                      <jats:italic>et al.<\/jats:italic>\n                    <\/jats:bold>\n                    (p.\n                    <jats:related-article xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" ext-link-type=\"doi\" page=\"229\" related-article-type=\"in-this-issue\" vol=\"335\" xlink:href=\"10.1126\/science.1214448\">229<\/jats:related-article>\n                    ) now show that the rhomboid family member iRhom2 interacts with TACE in macrophages and is required for its proper intracellular trafficking and activation. In the absence of iRhom2, TACE was not released from the endoplasmic reticulum, and active protease did not reach the cell surface. Because of an inability to produce TNF, iRhom2-deficient mice were more resistant to lipopolysaccharide-induced septic shock but could not adequately control a\n                    <jats:italic>Listeria monocytogenes<\/jats:italic>\n                    infection.\n                  <\/jats:p>","DOI":"10.1126\/science.1214448","type":"journal-article","created":{"date-parts":[[2012,1,12]],"date-time":"2012-01-12T14:53:59Z","timestamp":1326380039000},"page":"229-232","source":"Crossref","is-referenced-by-count":317,"title":["iRhom2 Regulation of TACE Controls TNF-Mediated Protection Against\n                    <i>Listeria<\/i>\n                    and Responses to LPS"],"prefix":"10.1126","volume":"335","author":[{"given":"David R.","family":"McIlwain","sequence":"first","affiliation":[{"name":"Campell Family Institute for Breast Cancer Research, Ontario Cancer Institute, University Health Network (UHN), 620 University Avenue, Toronto, Ontario M5G 2C1, Canada."},{"name":"Department of Medical Biophysics, University of Toronto, 1 King\u2032s Circle, Toronto, Ontario M5S 1A8, Canada."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Philipp A.","family":"Lang","sequence":"additional","affiliation":[{"name":"Campell Family Institute for Breast Cancer Research, Ontario Cancer Institute, University Health Network (UHN), 620 University Avenue, Toronto, Ontario M5G 2C1, Canada."},{"name":"Department of Gastroenterology, Hepatology and Infectious Diseases, University of D\u00fcsseldorf, Universit\u00e4tsstrasse 1, 40225 D\u00fcsseldorf, Germany."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thorsten","family":"Maretzky","sequence":"additional","affiliation":[{"name":"Arthritis and Tissue Degeneration Program, Hospital for Special Surgery, New York, NY 10021, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Koichi","family":"Hamada","sequence":"additional","affiliation":[{"name":"Okada Projects at the Center for AIDS Research, Kumamoto University, 2-2-1 Honjo, Kumamoto 860-0811, Japan."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kazuhito","family":"Ohishi","sequence":"additional","affiliation":[{"name":"Department of Pathology, Graduate School of Medicine, Osaka University, 2-2 Yamada-oka, Suita, Osaka 565-0871, Japan."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sathish Kumar","family":"Maney","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology, Hepatology and Infectious Diseases, University of D\u00fcsseldorf, Universit\u00e4tsstrasse 1, 40225 D\u00fcsseldorf, Germany."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thorsten","family":"Berger","sequence":"additional","affiliation":[{"name":"Campell Family Institute for Breast Cancer Research, Ontario Cancer Institute, University Health Network (UHN), 620 University Avenue, Toronto, Ontario M5G 2C1, Canada."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aditya","family":"Murthy","sequence":"additional","affiliation":[{"name":"Ontario Cancer Institute, UHN, Toronto, Ontario, M5G 2M9, Canada."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gordon","family":"Duncan","sequence":"additional","affiliation":[{"name":"Campell Family Institute for Breast Cancer Research, Ontario Cancer Institute, University Health Network (UHN), 620 University Avenue, Toronto, Ontario M5G 2C1, Canada."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Haifeng C.","family":"Xu","sequence":"additional","affiliation":[{"name":"Campell Family Institute for Breast Cancer Research, Ontario Cancer Institute, University Health Network (UHN), 620 University Avenue, Toronto, Ontario M5G 2C1, Canada."},{"name":"Department of Gastroenterology, Hepatology and Infectious Diseases, University of D\u00fcsseldorf, Universit\u00e4tsstrasse 1, 40225 D\u00fcsseldorf, Germany."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Karl S.","family":"Lang","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology, Hepatology and Infectious Diseases, University of D\u00fcsseldorf, Universit\u00e4tsstrasse 1, 40225 D\u00fcsseldorf, Germany."},{"name":"Institute for Immunology, University of Essen, Hufelandstrasse 55, 45147 Essen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dieter","family":"H\u00e4ussinger","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology, Hepatology and Infectious Diseases, University of D\u00fcsseldorf, Universit\u00e4tsstrasse 1, 40225 D\u00fcsseldorf, Germany."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrew","family":"Wakeham","sequence":"additional","affiliation":[{"name":"Campell Family Institute for Breast Cancer Research, Ontario Cancer Institute, University Health Network (UHN), 620 University Avenue, Toronto, Ontario M5G 2C1, Canada."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Annick","family":"Itie-Youten","sequence":"additional","affiliation":[{"name":"Campell Family Institute for Breast Cancer Research, Ontario Cancer Institute, University Health Network (UHN), 620 University Avenue, Toronto, Ontario M5G 2C1, Canada."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rama","family":"Khokha","sequence":"additional","affiliation":[{"name":"Ontario Cancer Institute, UHN, Toronto, Ontario, M5G 2M9, Canada."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pamela S.","family":"Ohashi","sequence":"additional","affiliation":[{"name":"Campell Family Institute for Breast Cancer Research, Ontario Cancer Institute, University Health Network (UHN), 620 University Avenue, Toronto, Ontario M5G 2C1, Canada."},{"name":"Department of Medical Biophysics, University of Toronto, 1 King\u2032s Circle, Toronto, Ontario M5S 1A8, 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