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http://purl.uniprot.org/citations/16009940http://www.w3.org/1999/02/22-rdf-syntax-ns#typehttp://purl.uniprot.org/core/Journal_Citation
http://purl.uniprot.org/citations/16009940http://www.w3.org/1999/02/22-rdf-syntax-ns#typehttp://purl.uniprot.org/core/Journal_Citation
http://purl.uniprot.org/citations/16009940http://www.w3.org/2000/01/rdf-schema#comment"IFN-alpha/beta plays an essential role in innate immunity against viral and bacterial infection. Among the proteins induced by IFN-alpha/beta are the ubiquitin-like ISG15 protein and its E1- (Ube1L) and E2-(UbcH8) conjugating enzymes, leading to the conjugation of ISG15 to cellular proteins. It is likely that ISG15 conjugation plays an important role in antiviral response because a human virus, influenza B virus, inhibits ISG15 conjugation. However, the biological function of ISG15 modification remains unknown, largely because only a few human ISG15 target proteins have been identified. Here we purify ISG15-modified proteins from IFN-beta-treated human (HeLa) cells by using double-affinity selection and use mass spectroscopy to identify a large number (158) of ISG15 target proteins. Eight of these proteins were subjected to further analysis and verified to be ISG15 modified in IFN-beta-treated cells, increasing the likelihood that most, if not all, targets identified by mass spectroscopy are bona fide ISG15 targets. Several of the targets are IFN-alpha/beta-induced antiviral proteins, including PKR, MxA, HuP56, and RIG-I, providing a rationale for the inhibition of ISG15 conjugation by influenza B virus. Most targets are constitutively expressed proteins that function in diverse cellular pathways, including RNA splicing, chromatin remodeling/polymerase II transcription, cytoskeleton organization and regulation, stress responses, and translation. These results indicate that ISG15 conjugation impacts nuclear as well as cytoplasmic functions. By targeting a wide array of constitutively expressed proteins, ISG15 conjugation greatly extends the repertoire of cellular functions that are affected by IFN-alpha/beta."xsd:string
http://purl.uniprot.org/citations/16009940http://purl.org/dc/terms/identifier"doi:10.1073/pnas.0504754102"xsd:string
http://purl.uniprot.org/citations/16009940http://purl.org/dc/terms/identifier"doi:10.1073/pnas.0504754102"xsd:string
http://purl.uniprot.org/citations/16009940http://purl.uniprot.org/core/author"Gygi S.P."xsd:string
http://purl.uniprot.org/citations/16009940http://purl.uniprot.org/core/author"Gygi S.P."xsd:string
http://purl.uniprot.org/citations/16009940http://purl.uniprot.org/core/author"Zhao C."xsd:string
http://purl.uniprot.org/citations/16009940http://purl.uniprot.org/core/author"Zhao C."xsd:string
http://purl.uniprot.org/citations/16009940http://purl.uniprot.org/core/author"Denison C."xsd:string
http://purl.uniprot.org/citations/16009940http://purl.uniprot.org/core/author"Denison C."xsd:string
http://purl.uniprot.org/citations/16009940http://purl.uniprot.org/core/author"Krug R.M."xsd:string
http://purl.uniprot.org/citations/16009940http://purl.uniprot.org/core/author"Krug R.M."xsd:string
http://purl.uniprot.org/citations/16009940http://purl.uniprot.org/core/author"Huibregtse J.M."xsd:string
http://purl.uniprot.org/citations/16009940http://purl.uniprot.org/core/author"Huibregtse J.M."xsd:string
http://purl.uniprot.org/citations/16009940http://purl.uniprot.org/core/date"2005"xsd:gYear
http://purl.uniprot.org/citations/16009940http://purl.uniprot.org/core/date"2005"xsd:gYear
http://purl.uniprot.org/citations/16009940http://purl.uniprot.org/core/name"Proc. Natl. Acad. Sci. U.S.A."xsd:string
http://purl.uniprot.org/citations/16009940http://purl.uniprot.org/core/name"Proc. Natl. Acad. Sci. U.S.A."xsd:string
http://purl.uniprot.org/citations/16009940http://purl.uniprot.org/core/pages"10200-10205"xsd:string
http://purl.uniprot.org/citations/16009940http://purl.uniprot.org/core/pages"10200-10205"xsd:string
http://purl.uniprot.org/citations/16009940http://purl.uniprot.org/core/title"Human ISG15 conjugation targets both IFN-induced and constitutively expressed proteins functioning in diverse cellular pathways."xsd:string
http://purl.uniprot.org/citations/16009940http://purl.uniprot.org/core/title"Human ISG15 conjugation targets both IFN-induced and constitutively expressed proteins functioning in diverse cellular pathways."xsd:string
http://purl.uniprot.org/citations/16009940http://purl.uniprot.org/core/volume"102"xsd:string
http://purl.uniprot.org/citations/16009940http://purl.uniprot.org/core/volume"102"xsd:string
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