| http://purl.uniprot.org/citations/24942588 | http://www.w3.org/1999/02/22-rdf-syntax-ns#type | http://purl.uniprot.org/core/Journal_Citation |
| http://purl.uniprot.org/citations/24942588 | http://www.w3.org/2000/01/rdf-schema#comment | "UnlabelledMurine cytomegalovirus (MCMV) rapidly induces activation of nuclear factor κB (NF-κB) upon infection of host cells. After a transient phase of activation, the MCMV M45 protein blocks all canonical NF-κB-activating pathways by inducing the degradation of the gamma subunit of the inhibitor of κB kinase complex (IKKγ; commonly referred to as the NF-κB essential modulator [NEMO]). Here we show that the viral M45 protein also mediates rapid NF-κB activation immediately after infection. MCMV mutants lacking M45 or expressing C-terminally truncated M45 proteins induced neither NF-κB activation nor transcription of NF-κB-dependent genes within the first 3 h of infection. Rapid NF-κB activation was absent in MCMV-infected NEMO-deficient fibroblasts, indicating that activation occurs at or upstream of the IKK complex. NF-κB activation was strongly reduced in murine fibroblasts lacking receptor-interacting protein 1 (RIP1), a known M45-interacting protein, but was restored upon complementation with murine RIP1. However, the ability of M45 to interact with RIP1 and NEMO was not sufficient to induce NF-κB activation upon infection. In addition, incorporation of the M45 protein into virions was required. This was dependent on a C-terminal region of M45, which is not required for interaction with RIP1 and NEMO. We propose a model in which M45 delivered by viral particles activates NF-κB, presumably involving an interaction with RIP1 and NEMO. Later in infection, expression of M45 induces the degradation of NEMO and the shutdown of canonical NF-κB activation.ImportanceTranscription factor NF-κB is an important regulator of innate and adaptive immunity. Its activation can be beneficial or detrimental for viral pathogens. Therefore, many viruses interfere with NF-κB signaling by stimulating or inhibiting the activation of this transcription factor. Cytomegaloviruses, opportunistic pathogens that cause lifelong infections in their hosts, activate NF-κB rapidly and transiently upon infection but block NF-κB signaling soon thereafter. Here we report the surprising finding that the murine cytomegalovirus protein M45, a component of viral particles, plays a dual role in NF-κB signaling. It not only blocks NF-κB signaling later in infection but also triggers the rapid activation of NF-κB immediately following virus entry into host cells. Both activation and inhibition involve M45 interaction with the cellular signaling mediators RIP1 and NEMO. Similar dual functions in NF-κB signaling are likely to be found in other viral proteins."xsd:string |
| http://purl.uniprot.org/citations/24942588 | http://purl.org/dc/terms/identifier | "doi:10.1128/jvi.00684-14"xsd:string |
| http://purl.uniprot.org/citations/24942588 | http://purl.uniprot.org/core/author | "Brune W."xsd:string |
| http://purl.uniprot.org/citations/24942588 | http://purl.uniprot.org/core/author | "Krause E."xsd:string |
| http://purl.uniprot.org/citations/24942588 | http://purl.uniprot.org/core/author | "de Graaf M."xsd:string |
| http://purl.uniprot.org/citations/24942588 | http://purl.uniprot.org/core/author | "Dolken L."xsd:string |
| http://purl.uniprot.org/citations/24942588 | http://purl.uniprot.org/core/author | "Fliss P.M."xsd:string |
| http://purl.uniprot.org/citations/24942588 | http://purl.uniprot.org/core/date | "2014"xsd:gYear |
| http://purl.uniprot.org/citations/24942588 | http://purl.uniprot.org/core/name | "J Virol"xsd:string |
| http://purl.uniprot.org/citations/24942588 | http://purl.uniprot.org/core/pages | "9963-9975"xsd:string |
| http://purl.uniprot.org/citations/24942588 | http://purl.uniprot.org/core/title | "Murine cytomegalovirus virion-associated protein M45 mediates rapid NF-kappaB activation after infection."xsd:string |
| http://purl.uniprot.org/citations/24942588 | http://purl.uniprot.org/core/volume | "88"xsd:string |
| http://purl.uniprot.org/citations/24942588 | http://www.w3.org/2004/02/skos/core#exactMatch | http://purl.uniprot.org/pubmed/24942588 |
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| http://purl.uniprot.org/uniprot/#_Q06A28-mappedCitation-24942588 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/24942588 |
| http://purl.uniprot.org/uniprot/#_P25799-mappedCitation-24942588 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/24942588 |
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