{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,1]],"date-time":"2026-04-01T20:02:27Z","timestamp":1775073747457,"version":"3.50.1"},"reference-count":26,"publisher":"American Association for the Advancement of Science (AAAS)","issue":"6065","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.1214400","type":"journal-article","created":{"date-parts":[[2012,1,12]],"date-time":"2012-01-12T14:53:59Z","timestamp":1326380039000},"page":"225-228","source":"Crossref","is-referenced-by-count":366,"title":["Tumor Necrosis Factor Signaling Requires iRhom2 to Promote Trafficking and Activation of TACE"],"prefix":"10.1126","volume":"335","author":[{"given":"Colin","family":"Adrain","sequence":"first","affiliation":[{"name":"Medical Research Council Laboratory of Molecular Biology, Hills Road, Cambridge CB2 0QH, UK."}]},{"given":"Markus","family":"Zettl","sequence":"additional","affiliation":[{"name":"Medical Research Council Laboratory of Molecular Biology, Hills Road, Cambridge CB2 0QH, UK."}]},{"given":"Yonka","family":"Christova","sequence":"additional","affiliation":[{"name":"Medical Research Council Laboratory of Molecular Biology, Hills Road, Cambridge CB2 0QH, UK."}]},{"given":"Neil","family":"Taylor","sequence":"additional","affiliation":[{"name":"Cambridge Research Institute, Cancer Research UK, Li Ka Shing Centre, Robinson Way, Cambridge CB2 0RE, UK."}]},{"given":"Matthew","family":"Freeman","sequence":"additional","affiliation":[{"name":"Medical Research Council Laboratory of Molecular Biology, Hills Road, Cambridge CB2 0QH, 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