| http://purl.uniprot.org/citations/24784232 | http://www.w3.org/1999/02/22-rdf-syntax-ns#type | http://purl.uniprot.org/core/Journal_Citation |
| http://purl.uniprot.org/citations/24784232 | http://www.w3.org/2000/01/rdf-schema#comment | "Interferon-α (IFN-α) is essential for antiviral immunity, but in the absence of matrix metalloproteinase-12 (MMP-12) or IκBα (encoded by NFKBIA) we show that IFN-α is retained in the cytosol of virus-infected cells and is not secreted. Our findings suggest that activated IκBα mediates the export of IFN-α from virus-infected cells and that the inability of cells in Mmp12(-/-) but not wild-type mice to express IκBα and thus export IFN-α makes coxsackievirus type B3 infection lethal and renders respiratory syncytial virus more pathogenic. We show here that after macrophage secretion, MMP-12 is transported into virus-infected cells. In HeLa cells MMP-12 is also translocated to the nucleus, where it binds to the NFKBIA promoter, driving transcription. We also identified dual-regulated substrates that are repressed both by MMP-12 binding to the substrate's gene exons and by MMP-12-mediated cleavage of the substrate protein itself. Whereas intracellular MMP-12 mediates NFKBIA transcription, leading to IFN-α secretion and host protection, extracellular MMP-12 cleaves off the IFN-α receptor 2 binding site of systemic IFN-α, preventing an unchecked immune response. Consistent with an unexpected role for MMP-12 in clearing systemic IFN-α, treatment of coxsackievirus type B3-infected wild-type mice with a membrane-impermeable MMP-12 inhibitor elevates systemic IFN-α levels and reduces viral replication in pancreas while sparing intracellular MMP-12. These findings suggest that inhibiting extracellular MMP-12 could be a new avenue for the development of antiviral treatments."xsd:string |
| http://purl.uniprot.org/citations/24784232 | http://purl.org/dc/terms/identifier | "doi:10.1038/nm.3508"xsd:string |
| http://purl.uniprot.org/citations/24784232 | http://purl.uniprot.org/core/author | "Luo Z."xsd:string |
| http://purl.uniprot.org/citations/24784232 | http://purl.uniprot.org/core/author | "Luo H."xsd:string |
| http://purl.uniprot.org/citations/24784232 | http://purl.uniprot.org/core/author | "Overall C.M."xsd:string |
| http://purl.uniprot.org/citations/24784232 | http://purl.uniprot.org/core/author | "Robertson A.G."xsd:string |
| http://purl.uniprot.org/citations/24784232 | http://purl.uniprot.org/core/author | "Butler G.S."xsd:string |
| http://purl.uniprot.org/citations/24784232 | http://purl.uniprot.org/core/author | "Dive V."xsd:string |
| http://purl.uniprot.org/citations/24784232 | http://purl.uniprot.org/core/author | "Georgiadis D."xsd:string |
| http://purl.uniprot.org/citations/24784232 | http://purl.uniprot.org/core/author | "Bilawchuk L.M."xsd:string |
| http://purl.uniprot.org/citations/24784232 | http://purl.uniprot.org/core/author | "Duan W."xsd:string |
| http://purl.uniprot.org/citations/24784232 | http://purl.uniprot.org/core/author | "Hegele R.G."xsd:string |
| http://purl.uniprot.org/citations/24784232 | http://purl.uniprot.org/core/author | "Marchant D.J."xsd:string |
| http://purl.uniprot.org/citations/24784232 | http://purl.uniprot.org/core/author | "Moraes T.J."xsd:string |
| http://purl.uniprot.org/citations/24784232 | http://purl.uniprot.org/core/author | "McManus B.M."xsd:string |
| http://purl.uniprot.org/citations/24784232 | http://purl.uniprot.org/core/author | "Ng J."xsd:string |
| http://purl.uniprot.org/citations/24784232 | http://purl.uniprot.org/core/author | "Dufour A."xsd:string |
| http://purl.uniprot.org/citations/24784232 | http://purl.uniprot.org/core/author | "Norris M.J."xsd:string |
| http://purl.uniprot.org/citations/24784232 | http://purl.uniprot.org/core/author | "Cheung C.T."xsd:string |
| http://purl.uniprot.org/citations/24784232 | http://purl.uniprot.org/core/author | "Devel L."xsd:string |
| http://purl.uniprot.org/citations/24784232 | http://purl.uniprot.org/core/author | "Granville D.J."xsd:string |
| http://purl.uniprot.org/citations/24784232 | http://purl.uniprot.org/core/author | "Ang L."xsd:string |
| http://purl.uniprot.org/citations/24784232 | http://purl.uniprot.org/core/author | "Karpov A."xsd:string |
| http://purl.uniprot.org/citations/24784232 | http://purl.uniprot.org/core/author | "Wadsworth S.J."xsd:string |