| http://purl.uniprot.org/citations/27523608 | http://www.w3.org/1999/02/22-rdf-syntax-ns#type | http://purl.uniprot.org/core/Journal_Citation |
| http://purl.uniprot.org/citations/27523608 | http://www.w3.org/1999/02/22-rdf-syntax-ns#type | http://purl.uniprot.org/core/Journal_Citation |
| http://purl.uniprot.org/citations/27523608 | http://www.w3.org/2000/01/rdf-schema#comment | "Methionine-1 (M1)-linked ubiquitin chains regulate the activity of NF-κB, immune homeostasis, and responses to infection. The importance of negative regulators of M1-linked chains in vivo remains poorly understood. Here, we show that the M1-specific deubiquitinase OTULIN is essential for preventing TNF-associated systemic inflammation in humans and mice. A homozygous hypomorphic mutation in human OTULIN causes a potentially fatal autoinflammatory condition termed OTULIN-related autoinflammatory syndrome (ORAS). Four independent OTULIN mouse models reveal that OTULIN deficiency in immune cells results in cell-type-specific effects, ranging from over-production of inflammatory cytokines and autoimmunity due to accumulation of M1-linked polyubiquitin and spontaneous NF-κB activation in myeloid cells to downregulation of M1-polyubiquitin signaling by degradation of LUBAC in B and T cells. Remarkably, treatment with anti-TNF neutralizing antibodies ameliorates inflammation in ORAS patients and rescues mouse phenotypes. Hence, OTULIN is critical for restraining life-threatening spontaneous inflammation and maintaining immune homeostasis."xsd:string |
| http://purl.uniprot.org/citations/27523608 | http://purl.org/dc/terms/identifier | "doi:10.1016/j.cell.2016.07.019"xsd:string |
| http://purl.uniprot.org/citations/27523608 | http://purl.org/dc/terms/identifier | "doi:10.1016/j.cell.2016.07.019"xsd:string |
| http://purl.uniprot.org/citations/27523608 | http://purl.uniprot.org/core/author | "Elliott P.R."xsd:string |
| http://purl.uniprot.org/citations/27523608 | http://purl.uniprot.org/core/author | "Elliott P.R."xsd:string |
| http://purl.uniprot.org/citations/27523608 | http://purl.uniprot.org/core/author | "Maher E.R."xsd:string |
| http://purl.uniprot.org/citations/27523608 | http://purl.uniprot.org/core/author | "Maher E.R."xsd:string |
| http://purl.uniprot.org/citations/27523608 | http://purl.uniprot.org/core/author | "Morgan N.V."xsd:string |
| http://purl.uniprot.org/citations/27523608 | http://purl.uniprot.org/core/author | "Morgan N.V."xsd:string |
| http://purl.uniprot.org/citations/27523608 | http://purl.uniprot.org/core/author | "Komander D."xsd:string |
| http://purl.uniprot.org/citations/27523608 | http://purl.uniprot.org/core/author | "Komander D."xsd:string |
| http://purl.uniprot.org/citations/27523608 | http://purl.uniprot.org/core/author | "Walker J.A."xsd:string |
| http://purl.uniprot.org/citations/27523608 | http://purl.uniprot.org/core/author | "Walker J.A."xsd:string |
| http://purl.uniprot.org/citations/27523608 | http://purl.uniprot.org/core/author | "Damgaard R.B."xsd:string |
| http://purl.uniprot.org/citations/27523608 | http://purl.uniprot.org/core/author | "Damgaard R.B."xsd:string |
| http://purl.uniprot.org/citations/27523608 | http://purl.uniprot.org/core/author | "Titheradge H.L."xsd:string |
| http://purl.uniprot.org/citations/27523608 | http://purl.uniprot.org/core/author | "Titheradge H.L."xsd:string |
| http://purl.uniprot.org/citations/27523608 | http://purl.uniprot.org/core/author | "McKenzie A.N."xsd:string |
| http://purl.uniprot.org/citations/27523608 | http://purl.uniprot.org/core/author | "McKenzie A.N."xsd:string |
| http://purl.uniprot.org/citations/27523608 | http://purl.uniprot.org/core/author | "McHale D."xsd:string |
| http://purl.uniprot.org/citations/27523608 | http://purl.uniprot.org/core/author | "McHale D."xsd:string |
| http://purl.uniprot.org/citations/27523608 | http://purl.uniprot.org/core/author | "Marco-Casanova P."xsd:string |
| http://purl.uniprot.org/citations/27523608 | http://purl.uniprot.org/core/author | "Marco-Casanova P."xsd:string |