{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T12:27:38Z","timestamp":1790684858094,"version":"4.1.0"},"reference-count":69,"publisher":"Frontiers Media SA","content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"DOI":"10.3389\/fimmu.2017.00399","type":"journal-article","created":{"date-parts":[[2017,4,25]],"date-time":"2017-04-25T10:32:25Z","timestamp":1493116345000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":204,"title":["NF-\u03baB Pathway in Autoinflammatory Diseases: Dysregulation of Protein Modifications by Ubiquitin Defines a New Category of Autoinflammatory Diseases"],"prefix":"10.3389","volume":"8","author":[{"given":"Ivona","family":"Aksentijevich","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qing","family":"Zhou","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2017,4,19]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"203","DOI":"10.1146\/annurev-biochem-060310-170328","article-title":"The ubiquitin code","volume":"81","author":"Komander","year":"2012","journal-title":"Annu Rev Biochem"},{"key":"B2","doi-asserted-by":"publisher","first-page":"755","DOI":"10.1038\/nrm2780","article-title":"Building ubiquitin chains: E2 enzymes at work","volume":"10","author":"Ye","year":"2009","journal-title":"Nat Rev Mol Cell Biol"},{"key":"B3","doi-asserted-by":"publisher","first-page":"15247","DOI":"10.1073\/pnas.1314715110","article-title":"Activation of the canonical IKK complex by K63\/M1-linked hybrid ubiquitin chains","volume":"110","author":"Emmerich","year":"2013","journal-title":"Proc Natl Acad Sci U S A"},{"key":"B4","doi-asserted-by":"publisher","first-page":"399","DOI":"10.1038\/cr.2016.39","article-title":"Ubiquitin modifications","volume":"26","author":"Swatek","year":"2016","journal-title":"Cell Res"},{"key":"B5","doi-asserted-by":"publisher","first-page":"425","DOI":"10.1146\/annurev.biochem.67.1.425","article-title":"The ubiquitin system","volume":"67","author":"Hershko","year":"1998","journal-title":"Annu Rev Biochem"},{"key":"B6","doi-asserted-by":"publisher","first-page":"355","DOI":"10.1016\/j.tibs.2011.04.004","article-title":"Emerging roles for Lys11-linked polyubiquitin in cellular regulation","volume":"36","author":"Bremm","year":"2011","journal-title":"Trends Biochem Sci"},{"key":"B7","doi-asserted-by":"publisher","first-page":"95","DOI":"10.1111\/j.1600-065X.2012.01108.x","article-title":"Ubiquitination in signaling to and activation of IKK","volume":"246","author":"Chen","year":"2012","journal-title":"Immunol Rev"},{"key":"B8","doi-asserted-by":"publisher","first-page":"4337","DOI":"10.1111\/febs.12944","article-title":"Met1-linked ubiquitination in immune signalling","volume":"281","author":"Fiil","year":"2014","journal-title":"FEBS J"},{"key":"B9","doi-asserted-by":"publisher","first-page":"503","DOI":"10.1038\/nrm3836","article-title":"Linear ubiquitin chains: NF-kappa B signalling, cell death and beyond","volume":"15","author":"Iwai","year":"2014","journal-title":"Nat Rev Mol Cell Biol"},{"key":"B10","doi-asserted-by":"publisher","first-page":"190","DOI":"10.1111\/imr.12309","article-title":"Linear ubiquitination in immunity","volume":"266","author":"Shimizu","year":"2015","journal-title":"Immunol Rev"},{"key":"B11","doi-asserted-by":"publisher","first-page":"550","DOI":"10.1038\/nrm2731","article-title":"Breaking the chains: structure and function of the deubiquitinases","volume":"10","author":"Komander","year":"2009","journal-title":"Nat Rev Mol Cell Biol"},{"key":"B12","doi-asserted-by":"publisher","first-page":"107","DOI":"10.1111\/j.1600-065X.2012.01100.x","article-title":"Regulation of NF-kappa B by deubiquitinases","volume":"246","author":"Harhaj","year":"2012","journal-title":"Immunol Rev"},{"key":"B13","doi-asserted-by":"publisher","first-page":"895","DOI":"10.1002\/art.33368","article-title":"Mutations in proteasome subunit ss type 8 cause chronic atypical neutrophilic dermatosis with lipodystrophy and elevated temperature with evidence of genetic and phenotypic heterogeneity","volume":"64","author":"Liu","year":"2012","journal-title":"Arthritis Rheum"},{"key":"B14","doi-asserted-by":"publisher","first-page":"1178","DOI":"10.1038\/ni.2457","article-title":"Immunodeficiency, autoinflammation and amylopectinosis in humans with inherited HOIL-1 and LUBAC deficiency","volume":"13","author":"Boisson","year":"2012","journal-title":"Nat Immunol"},{"key":"B15","doi-asserted-by":"publisher","first-page":"939","DOI":"10.1084\/jem.20141130","article-title":"Human HOIP and LUBAC deficiency underlies autoinflammation, immunodeficiency, amylopectinosis, and lymphangiectasia","volume":"212","author":"Boisson","year":"2015","journal-title":"J Exp Med"},{"key":"B16","doi-asserted-by":"publisher","first-page":"67","DOI":"10.1038\/ng.3459","article-title":"Loss-of-function mutations in TNFAIP3 leading to A20 haploinsufficiency cause an early-onset autoinflammatory disease","volume":"48","author":"Zhou","year":"2016","journal-title":"Nat Genet"},{"key":"B17","doi-asserted-by":"publisher","first-page":"10127","DOI":"10.1073\/pnas.1612594113","article-title":"Biallelic hypomorphic mutations in a linear deubiquitinase define otulipenia, an early-onset autoinflammatory disease","volume":"113","author":"Zhou","year":"2016","journal-title":"Proc Natl Acad Sci U S A"},{"key":"B18","doi-asserted-by":"publisher","first-page":"1215","DOI":"10.1016\/j.cell.2016.07.019","article-title":"The deubiquitinase OTULIN is an essential negative regulator of inflammation and autoimmunity","volume":"166","author":"Damgaard","year":"2016","journal-title":"Cell"},{"key":"B19","doi-asserted-by":"publisher","first-page":"591","DOI":"10.1038\/nature09816","article-title":"Linear ubiquitination prevents inflammation and regulates immune signalling","volume":"471","author":"Gerlach","year":"2011","journal-title":"Nature"},{"key":"B20","doi-asserted-by":"publisher","first-page":"1098","DOI":"10.1016\/j.cell.2009.03.007","article-title":"Specific recognition of linear ubiquitin chains by NEMO is important for NF-kappa B activation","volume":"136","author":"Rahighi","year":"2009","journal-title":"Cell"},{"key":"B21","doi-asserted-by":"publisher","first-page":"123","DOI":"10.1038\/ncb1821","article-title":"Involvement of linear polyubiquitylation of NEMO in NF-kappa B activation","volume":"11","author":"Tokunaga","year":"2009","journal-title":"Nat Cell Biol"},{"key":"B22","doi-asserted-by":"publisher","first-page":"1312","DOI":"10.1016\/j.cell.2013.05.014","article-title":"OTULIN antagonizes LUBAC signaling by specifically hydrolyzing Met1-linked polyubiquitin","volume":"153","author":"Keusekotten","year":"2013","journal-title":"Cell"},{"key":"B23","doi-asserted-by":"publisher","first-page":"349","DOI":"10.1016\/j.molcel.2014.03.016","article-title":"Binding of OTULIN to the PUB domain of HOIP controls NF-kappa B signaling","volume":"54","author":"Schaeffer","year":"2014","journal-title":"Mol Cell"},{"key":"B24","doi-asserted-by":"publisher","first-page":"335","DOI":"10.1016\/j.molcel.2014.03.018","article-title":"Molecular basis and regulation of OTULIN-LUBAC interaction","volume":"54","author":"Elliott","year":"2014","journal-title":"Mol Cell"},{"key":"B25","doi-asserted-by":"publisher","first-page":"26","DOI":"10.1038\/ni.3618","article-title":"The signaling adaptor TRAF1 negatively regulates toll-like receptor signaling and this underlies its role in rheumatic disease","volume":"18","author":"Abdul-Sater","year":"2017","journal-title":"Nat Immunol"},{"key":"B26","doi-asserted-by":"publisher","first-page":"153","DOI":"10.1016\/j.celrep.2014.08.066","article-title":"HOIP deficiency causes embryonic lethality by aberrant TNFR1-mediated endothelial cell death","volume":"9","author":"Peltzer","year":"2014","journal-title":"Cell Rep"},{"key":"B27","doi-asserted-by":"crossref","first-page":"3890","DOI":"10.4049\/jimmunol.162.7.3890","article-title":"Absence of Peyer\u2019s patches and abnormal lymphoid architecture in chronic proliferative dermatitis (cpdm\/cpdm) mice","volume":"162","author":"HogenEsch","year":"1999","journal-title":"J Immunol"},{"key":"B28","doi-asserted-by":"publisher","first-page":"e85666","DOI":"10.1371\/journal.pone.0085666","article-title":"Chronic proliferative dermatitis in Sharpin null mice: development of an autoinflammatory disease in the absence of B and T lymphocytes and IL4\/IL13 signaling","volume":"9","author":"Potter","year":"2014","journal-title":"PLoS One"},{"key":"B29","doi-asserted-by":"publisher","DOI":"10.7554\/eLife.03422","article-title":"Sharpin prevents skin inflammation by inhibiting TNFR1-induced keratinocyte apoptosis","volume":"3","author":"Kumari","year":"2014","journal-title":"Elife"},{"key":"B30","doi-asserted-by":"publisher","DOI":"10.7554\/eLife.03464","article-title":"TNFR1-dependent cell death drives inflammation in Sharpin-deficient mice","volume":"3","author":"Rickard","year":"2014","journal-title":"Elife"},{"key":"B31","doi-asserted-by":"publisher","first-page":"2463","DOI":"10.1038\/emboj.2013.184","article-title":"Defective immune responses in mice lacking LUBAC-mediated linear ubiquitination in B cells","volume":"32","author":"Sasaki","year":"2013","journal-title":"EMBO J"},{"key":"B32","doi-asserted-by":"publisher","first-page":"36135","DOI":"10.1038\/srep36135","article-title":"Survival of mature T cells depends on signaling through HOIP","volume":"6","author":"Okamura","year":"2016","journal-title":"Sci Rep"},{"key":"B33","doi-asserted-by":"publisher","first-page":"318","DOI":"10.1038\/nature12296","article-title":"The linear ubiquitin-specific deubiquitinase gumby regulates angiogenesis","volume":"498","author":"Rivkin","year":"2013","journal-title":"Nature"},{"key":"B34","doi-asserted-by":"publisher","first-page":"2671","DOI":"10.1084\/jem.20160041","article-title":"LUBAC deficiency perturbs TLR3 signaling to cause immunodeficiency and autoinflammation","volume":"213","author":"Zinngrebe","year":"2016","journal-title":"J Exp Med"},{"key":"B35","doi-asserted-by":"publisher","DOI":"10.1016\/j.jaci.2016.09.038","article-title":"Haploinsufficiency of TNFAIP3 (A20) by germline mutation is involved in autoimmune lymphoproliferative syndrome","author":"Takagi","year":"2016","journal-title":"J Allergy Clin Immunol"},{"key":"B36","doi-asserted-by":"publisher","first-page":"146","DOI":"10.1016\/j.alit.2016.06.006","article-title":"A Japanese family case with juvenile onset Behcet\u2019s disease caused by TNFAIP3 mutation","volume":"66","author":"Ohnishi","year":"2016","journal-title":"Allergol Int"},{"key":"B37","doi-asserted-by":"publisher","first-page":"e000223","DOI":"10.1136\/rmdopen-2015-000223","article-title":"Novel heterozygous C243Y A20\/TNFAIP3 gene mutation is responsible for chronic inflammation in autosomal-dominant Behcet\u2019s disease","volume":"2","author":"Shigemura","year":"2016","journal-title":"RMD Open"},{"key":"B38","doi-asserted-by":"publisher","first-page":"853","DOI":"10.1016\/S0092-8674(00)81064-8","article-title":"Site-specific phosphorylation of IkappaBalpha by a novel ubiquitination-dependent protein kinase activity","volume":"84","author":"Chen","year":"1996","journal-title":"Cell"},{"key":"B39","doi-asserted-by":"publisher","first-page":"4","DOI":"10.1016\/j.coi.2012.12.005","article-title":"Regulation of NF-kappaB by ubiquitination","volume":"25","author":"Chen","year":"2013","journal-title":"Curr Opin Immunol"},{"key":"B40","doi-asserted-by":"publisher","first-page":"55","DOI":"10.1016\/j.immuni.2014.12.031","article-title":"A20 restricts ubiquitination of pro-interleukin-1beta protein complexes and suppresses NLRP3 inflammasome activity","volume":"42","author":"Duong","year":"2015","journal-title":"Immunity"},{"key":"B41","doi-asserted-by":"publisher","first-page":"26107","DOI":"10.1074\/jbc.M111.233163","article-title":"NF-kappaB essential modulator (NEMO) interaction with linear and lys-63 ubiquitin chains contributes to NF-kappaB activation","volume":"286","author":"Hadian","year":"2011","journal-title":"J Biol Chem"},{"key":"B42","doi-asserted-by":"publisher","first-page":"8217","DOI":"10.1074\/jbc.R800032200","article-title":"A20: central gatekeeper in inflammation and immunity","volume":"284","author":"Coornaert","year":"2009","journal-title":"J Biol Chem"},{"key":"B43","doi-asserted-by":"publisher","first-page":"22","DOI":"10.1016\/j.it.2013.10.005","article-title":"A20 in inflammation and autoimmunity","volume":"35","author":"Catrysse","year":"2014","journal-title":"Trends Immunol"},{"key":"B44","doi-asserted-by":"publisher","first-page":"383","DOI":"10.1016\/j.it.2009.05.007","article-title":"The ubiquitin-editing enzyme A20 (TNFAIP3) is a central regulator of immunopathology","volume":"30","author":"Vereecke","year":"2009","journal-title":"Trends Immunol"},{"key":"B45","doi-asserted-by":"publisher","first-page":"7451","DOI":"10.1128\/MCB.01101-07","article-title":"IkappaB kinase beta phosphorylates the K63 deubiquitinase A20 to cause feedback inhibition of the NF-kappaB pathway","volume":"27","author":"Hutti","year":"2007","journal-title":"Mol Cell Biol"},{"key":"B46","doi-asserted-by":"publisher","first-page":"263","DOI":"10.1038\/ni1561","article-title":"T cell antigen receptor stimulation induces MALT1 paracaspase-mediated cleavage of the NF-kappaB inhibitor A20","volume":"9","author":"Coornaert","year":"2008","journal-title":"Nat Immunol"},{"key":"B47","doi-asserted-by":"publisher","first-page":"717","DOI":"10.1038\/nature07968","article-title":"Mutations of multiple genes cause deregulation of NF-kappaB in diffuse large B-cell lymphoma","volume":"459","author":"Compagno","year":"2009","journal-title":"Nature"},{"key":"B48","doi-asserted-by":"publisher","first-page":"981","DOI":"10.1084\/jem.20090528","article-title":"TNFAIP3 (A20) is a tumor suppressor gene in Hodgkin lymphoma and primary mediastinal B cell lymphoma","volume":"206","author":"Schmitz","year":"2009","journal-title":"J Exp Med"},{"key":"B49","doi-asserted-by":"publisher","first-page":"1059","DOI":"10.1038\/ng.200","article-title":"Genetic variants near TNFAIP3 on 6q23 are associated with systemic lupus erythematosus","volume":"40","author":"Graham","year":"2008","journal-title":"Nat Genet"},{"key":"B50","doi-asserted-by":"publisher","first-page":"1062","DOI":"10.1038\/ng.202","article-title":"Multiple polymorphisms in the TNFAIP3 region are independently associated with systemic lupus erythematosus","volume":"40","author":"Musone","year":"2008","journal-title":"Nat Genet"},{"key":"B51","doi-asserted-by":"publisher","first-page":"253","DOI":"10.1038\/ng.766","article-title":"Association of a functional variant downstream of TNFAIP3 with systemic lupus erythematosus","volume":"43","author":"Adrianto","year":"2011","journal-title":"Nat Genet"},{"key":"B52","doi-asserted-by":"publisher","first-page":"1431","DOI":"10.1038\/ng.2007.32","article-title":"Rheumatoid arthritis association at 6q23","volume":"39","author":"Thomson","year":"2007","journal-title":"Nat Genet"},{"key":"B53","doi-asserted-by":"publisher","first-page":"199","DOI":"10.1038\/ng.311","article-title":"Genome-wide scan reveals association of psoriasis with IL-23 and NF-kappaB pathways","volume":"41","author":"Nair","year":"2009","journal-title":"Nat Genet"},{"key":"B54","doi-asserted-by":"publisher","first-page":"188","DOI":"10.1038\/gene.2008.99","article-title":"Analysis of 17 autoimmune disease-associated variants in type 1 diabetes identifies 6q23\/TNFAIP3 as a susceptibility locus","volume":"10","author":"Fung","year":"2009","journal-title":"Genes Immun"},{"key":"B55","doi-asserted-by":"publisher","first-page":"1078","DOI":"10.1136\/gut.2008.169052","article-title":"Coeliac disease-associated risk variants in TNFAIP3 and REL implicate altered NF-kappaB signalling","volume":"58","author":"Trynka","year":"2009","journal-title":"Gut"},{"key":"B56","doi-asserted-by":"publisher","first-page":"499","DOI":"10.2337\/db06-0946","article-title":"Tag polymorphisms at the A20 (TNFAIP3) locus are associated with lower gene expression and increased risk of coronary artery disease in type 2 diabetes","volume":"56","author":"Boonyasrisawat","year":"2007","journal-title":"Diabetes"},{"key":"B57","doi-asserted-by":"publisher","first-page":"7001","DOI":"10.4049\/jimmunol.1000324","article-title":"African-derived genetic polymorphisms in TNFAIP3 mediate risk for autoimmunity","volume":"184","author":"Lodolce","year":"2010","journal-title":"J Immunol"},{"key":"B58","doi-asserted-by":"publisher","first-page":"861","DOI":"10.1016\/j.jaci.2012.04.041","article-title":"Genome-wide association studies of asthma indicate opposite immunopathogenesis direction from autoimmune diseases","volume":"130","author":"Li","year":"2012","journal-title":"J Allergy Clin Immunol"},{"key":"B59","doi-asserted-by":"publisher","first-page":"1106","DOI":"10.1126\/science.aac6623","article-title":"Farm dust and endotoxin protect against allergy through A20 induction in lung epithelial cells","volume":"349","author":"Schuijs","year":"2015","journal-title":"Science"},{"key":"B60","doi-asserted-by":"publisher","first-page":"120","DOI":"10.1038\/gene.2014.75","article-title":"Meta-analysis of the TNFAIP3 region in psoriasis reveals a risk haplotype that is distinct from other autoimmune diseases","volume":"16","author":"Nititham","year":"2015","journal-title":"Genes Immun"},{"key":"B61","doi-asserted-by":"publisher","first-page":"2350","DOI":"10.1126\/science.289.5488.2350","article-title":"Failure to regulate TNF-induced NF-kappaB and cell death responses in A20-deficient mice","volume":"289","author":"Lee","year":"2000","journal-title":"Science"},{"key":"B62","doi-asserted-by":"publisher","first-page":"1052","DOI":"10.1038\/ni1110","article-title":"The ubiquitin-modifying enzyme A20 is required for termination of toll-like receptor responses","volume":"5","author":"Boone","year":"2004","journal-title":"Nat Immunol"},{"key":"B63","doi-asserted-by":"publisher","first-page":"822","DOI":"10.1038\/ng.916","article-title":"A20 edits ubiquitin and autoimmune paradigms","volume":"43","author":"Martin","year":"2011","journal-title":"Nat Genet"},{"key":"B64","doi-asserted-by":"publisher","first-page":"559","DOI":"10.1016\/j.molcel.2011.09.015","article-title":"Direct, noncatalytic mechanism of IKK inhibition by A20","volume":"44","author":"Skaug","year":"2011","journal-title":"Mol Cell"},{"key":"B65","doi-asserted-by":"publisher","first-page":"896","DOI":"10.1016\/j.immuni.2013.03.008","article-title":"Dimerization and ubiquitin mediated recruitment of A20, a complex deubiquitinating enzyme","volume":"38","author":"Lu","year":"2013","journal-title":"Immunity"},{"key":"B66","doi-asserted-by":"publisher","first-page":"69","DOI":"10.1038\/nature13322","article-title":"Negative regulation of the NLRP3 inflammasome by A20 protects against arthritis","volume":"512","author":"Vande Walle","year":"2014","journal-title":"Nature"},{"key":"B67","doi-asserted-by":"publisher","first-page":"63","DOI":"10.3389\/fnmol.2014.00063","article-title":"Ubiquitin pathways in neurodegenerative disease","volume":"7","author":"Atkin","year":"2014","journal-title":"Front Mol Neurosci"},{"key":"B68","doi-asserted-by":"publisher","first-page":"538","DOI":"10.1186\/s12885-016-2575-8","article-title":"Atypical ubiquitin ligase RNF31: the nuclear factor modulator in breast cancer progression","volume":"16","author":"Zhu","year":"2016","journal-title":"BMC Cancer"},{"key":"B69","doi-asserted-by":"publisher","first-page":"494","DOI":"10.1016\/j.ccell.2016.03.006","article-title":"Targeting non-proteolytic protein ubiquitination for the treatment of diffuse large B cell lymphoma","volume":"29","author":"Yang","year":"2016","journal-title":"Cancer Cell"}],"container-title":["Frontiers in Immunology"],"original-title":[],"link":[{"URL":"http:\/\/journal.frontiersin.org\/article\/10.3389\/fimmu.2017.00399\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,8,23]],"date-time":"2023-08-23T07:54:53Z","timestamp":1692777293000},"score":1,"resource":{"primary":{"URL":"http:\/\/journal.frontiersin.org\/article\/10.3389\/fimmu.2017.00399\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2017,4,19]]},"references-count":69,"alternative-id":["10.3389\/fimmu.2017.00399"],"URL":"https:\/\/doi.org\/10.3389\/fimmu.2017.00399","relation":{},"ISSN":["1664-3224"],"issn-type":[{"value":"1664-3224","type":"electronic"}],"subject":[],"published":{"date-parts":[[2017,4,19]]},"article-number":"399"}}