{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,20]],"date-time":"2026-10-20T18:47:00Z","timestamp":1792522020528,"version":"4.5.0"},"reference-count":19,"publisher":"National Academy of Sciences","issue":"36","content-domain":{"domain":["www.pnas.org"],"crossmark-restriction":true},"short-container-title":["Proc. Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[2016,9,6]]},"abstract":"<jats:title>Significance<\/jats:title>\n                  <jats:p>We describe a human disease linked to mutations in the linear deubiquitinase (DUB) OTULIN, which functions as a Met1-specific DUB to remove linear polyubiquitin chains that are assembled by the linear ubiquitin assembly complex (LUBAC). OTULIN has a role in regulating Wnt and innate immune signaling complexes. Hydrolysis of Met1-linked ubiquitin chains attenuates inflammatory signals in the NF-\u03baB and ASC-mediated pathways. OTULIN-deficient patients have excessive linear ubiquitination of target proteins, such as NEMO, RIPK1, TNFR1, and ASC, leading to severe inflammation. Cytokine inhibitors have been efficient in suppressing constitutive inflammation in these patients. This study, together with the identification of haploinsufficiency of A20 (HA20), suggests a category of human inflammatory diseases, diseases of dysregulated ubiquitination.<\/jats:p>","DOI":"10.1073\/pnas.1612594113","type":"journal-article","created":{"date-parts":[[2016,8,24]],"date-time":"2016-08-24T23:08:49Z","timestamp":1472080129000},"page":"10127-10132","update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":276,"title":["Biallelic hypomorphic mutations in a linear deubiquitinase define otulipenia, an early-onset autoinflammatory disease"],"prefix":"10.1073","volume":"113","author":[{"given":"Qing","family":"Zhou","sequence":"first","affiliation":[{"name":"Inflammatory Disease Section, National Human Genome Research Institute, Bethesda, MD 20892;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaomin","family":"Yu","sequence":"additional","affiliation":[{"name":"Genetics and Pathogenesis of Allergy Section, 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Turkey;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joshua D.","family":"Milner","sequence":"additional","affiliation":[{"name":"Genetics and Pathogenesis of Allergy Section, Laboratory of Allergic Diseases, National Institute of Allergy and Infectious Diseases, Bethesda, MD 20892;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Manfred","family":"Boehm","sequence":"additional","affiliation":[{"name":"Laboratory of Cardiovascular Regenerative Medicine, National Heart, Lung, and Blood Institute, Bethesda, MD 20892;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sergio D.","family":"Rosenzweig","sequence":"additional","affiliation":[{"name":"Department of Laboratory Medicine, National Institutes of Health Clinical Center, Bethesda, MD 20892;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Massimo","family":"Gadina","sequence":"additional","affiliation":[{"name":"Translational Immunology Section, National Institute 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