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http://purl.uniprot.org/citations/24114841http://www.w3.org/1999/02/22-rdf-syntax-ns#typehttp://purl.uniprot.org/core/Journal_Citation
http://purl.uniprot.org/citations/24114841http://www.w3.org/2000/01/rdf-schema#comment"Vaccinia virus encodes a number of proteins that inhibit and manipulate innate immune signaling pathways that also have a role in virulence. These include A52, a protein shown to inhibit IL-1- and Toll-like receptor-stimulated NFκB activation, via interaction with interleukin-1 receptor-associated kinase 2 (IRAK2). Interestingly, A52 was also found to activate p38 MAPK and thus enhance Toll-like receptor-dependent IL-10 induction, which was TRAF6-dependent, but the manner in which A52 manipulates TRAF6 to stimulate p38 activation was unclear. Here, we show that A52 has a non-canonical TRAF6-binding motif that is essential for TRAF6 binding and p38 activation but dispensable for NFκB inhibition and IRAK2 interaction. Wild-type A52, but not a mutant defective in p38 activation and TRAF6 binding (F154A), caused TRAF6 oligomerization and subsequent TRAF6-TAK1 association. The crystal structure of A52 shows that it adopts a Bcl2-like fold and exists as a dimer in solution. Residue Met-65 was identified as being located in the A52 dimer interface, and consistent with that, A52-M65E was impaired in its ability to dimerize. A52-M65E although capable of interacting with TRAF6, was unable to cause either TRAF6 self-association, induce the TRAF6-TAK1 association, or activate p38 MAPK. The results suggest that an A52 dimer causes TRAF6 self-association, leading to TAK1 recruitment and p38 activation. This reveals a molecular mechanism whereby poxviruses manipulate TRAF6 to activate MAPKs (which can be proviral) without stimulating antiviral NFκB activation."xsd:string
http://purl.uniprot.org/citations/24114841http://purl.org/dc/terms/identifier"doi:10.1074/jbc.m113.485490"xsd:string
http://purl.uniprot.org/citations/24114841http://purl.uniprot.org/core/author"Bowie A.G."xsd:string
http://purl.uniprot.org/citations/24114841http://purl.uniprot.org/core/author"Rupp S."xsd:string
http://purl.uniprot.org/citations/24114841http://purl.uniprot.org/core/author"Khan A.R."xsd:string
http://purl.uniprot.org/citations/24114841http://purl.uniprot.org/core/author"Oda S.I."xsd:string
http://purl.uniprot.org/citations/24114841http://purl.uniprot.org/core/author"Brennan K."xsd:string
http://purl.uniprot.org/citations/24114841http://purl.uniprot.org/core/author"Stack J."xsd:string
http://purl.uniprot.org/citations/24114841http://purl.uniprot.org/core/author"Flannery S.M."xsd:string
http://purl.uniprot.org/citations/24114841http://purl.uniprot.org/core/author"Hurst T.P."xsd:string
http://purl.uniprot.org/citations/24114841http://purl.uniprot.org/core/date"2013"xsd:gYear
http://purl.uniprot.org/citations/24114841http://purl.uniprot.org/core/name"J Biol Chem"xsd:string
http://purl.uniprot.org/citations/24114841http://purl.uniprot.org/core/pages"33642-33653"xsd:string
http://purl.uniprot.org/citations/24114841http://purl.uniprot.org/core/title"Poxviral protein A52 stimulates p38 mitogen-activated protein kinase (MAPK) activation by causing tumor necrosis factor receptor-associated factor 6 (TRAF6) self-association leading to transforming growth factor beta-activated kinase 1 (TAK1) recruitment."xsd:string
http://purl.uniprot.org/citations/24114841http://purl.uniprot.org/core/volume"288"xsd:string
http://purl.uniprot.org/citations/24114841http://www.w3.org/2004/02/skos/core#exactMatchhttp://purl.uniprot.org/pubmed/24114841
http://purl.uniprot.org/citations/24114841http://xmlns.com/foaf/0.1/primaryTopicOfhttps://pubmed.ncbi.nlm.nih.gov/24114841
http://purl.uniprot.org/uniprot/#_A0A3B2WAZ7-mappedCitation-24114841http://www.w3.org/1999/02/22-rdf-syntax-ns#objecthttp://purl.uniprot.org/citations/24114841
http://purl.uniprot.org/uniprot/#_A0A3B2WB60-mappedCitation-24114841http://www.w3.org/1999/02/22-rdf-syntax-ns#objecthttp://purl.uniprot.org/citations/24114841
http://purl.uniprot.org/uniprot/#_A2AP92-mappedCitation-24114841http://www.w3.org/1999/02/22-rdf-syntax-ns#objecthttp://purl.uniprot.org/citations/24114841
http://purl.uniprot.org/uniprot/#_A2AP93-mappedCitation-24114841http://www.w3.org/1999/02/22-rdf-syntax-ns#objecthttp://purl.uniprot.org/citations/24114841
http://purl.uniprot.org/uniprot/#_B2KF34-mappedCitation-24114841http://www.w3.org/1999/02/22-rdf-syntax-ns#objecthttp://purl.uniprot.org/citations/24114841
http://purl.uniprot.org/uniprot/#_Q62073-mappedCitation-24114841http://www.w3.org/1999/02/22-rdf-syntax-ns#objecthttp://purl.uniprot.org/citations/24114841
http://purl.uniprot.org/uniprot/#_Q3TXG1-mappedCitation-24114841http://www.w3.org/1999/02/22-rdf-syntax-ns#objecthttp://purl.uniprot.org/citations/24114841