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Article: Involvement of the double-stranded-RNA-dependent kinase PKR in interferon expression and interferon-mediated antiviral activity

TitleInvolvement of the double-stranded-RNA-dependent kinase PKR in interferon expression and interferon-mediated antiviral activity
Authors
Issue Date1995
PublisherNational Academy of Sciences. The Journal's web site is located at http://www.pnas.org
Citation
Proceedings Of The National Academy Of Sciences Of The United States Of America, 1995, v. 92 n. 19, p. 8841-8845 How to Cite?
AbstractThe signaling mechanisms responsible for the induced expression of interferon (IFN) genes by vital infection or double-stranded RNA (dsRNA) are not well understood. Here we investigate the role of the interferon-induced dsRNA-dependent protein kinase PKR in the regulation of IFN induction. Biological activities attributed to PKR include regulating protein synthesis, mediating IFN actions, and functioning as a possible tumor suppressor. Since binding of dsRNA is required for its activation, PKR has been considered as a candidate signal transducer for regulating IFN expression. To examine this role of PKR, loss-of-function phenotypes in stable transformants of promonocytic U-937 cells were achieved by two different strategies, overexpression of an antisense PKR transcript or a dominant negative PKR mutant gene. Both types of PKR-deficient cells were more permissive for viral replication than the control U-937 cells. As the result of PKR loss, they also showed impaired induction of IFN-α and IFN-β genes in response to several inducers-specifically, encephalomyocarditis virus, lipopolysaccharide, and phorbol 12-myristate 13-acetate. Interestingly, while IFN-α induction by dsRNA was impaired in PKR-deficient cells, IFN-β induction remained intact. Loss of PKR function also resulted in decreased antiviral activity as elicited by IFN-α and, to a greater extent, by IFN- γ. These results implicate PKR in the regulation of several antiviral activities.
Persistent Identifierhttp://hdl.handle.net/10722/170280
ISSN
2015 Impact Factor: 9.423
2015 SCImago Journal Rankings: 6.883
ISI Accession Number ID

 

DC FieldValueLanguage
dc.contributor.authorDer, SDen_US
dc.contributor.authorLau, ASen_US
dc.date.accessioned2012-10-30T06:07:12Z-
dc.date.available2012-10-30T06:07:12Z-
dc.date.issued1995en_US
dc.identifier.citationProceedings Of The National Academy Of Sciences Of The United States Of America, 1995, v. 92 n. 19, p. 8841-8845en_US
dc.identifier.issn0027-8424en_US
dc.identifier.urihttp://hdl.handle.net/10722/170280-
dc.description.abstractThe signaling mechanisms responsible for the induced expression of interferon (IFN) genes by vital infection or double-stranded RNA (dsRNA) are not well understood. Here we investigate the role of the interferon-induced dsRNA-dependent protein kinase PKR in the regulation of IFN induction. Biological activities attributed to PKR include regulating protein synthesis, mediating IFN actions, and functioning as a possible tumor suppressor. Since binding of dsRNA is required for its activation, PKR has been considered as a candidate signal transducer for regulating IFN expression. To examine this role of PKR, loss-of-function phenotypes in stable transformants of promonocytic U-937 cells were achieved by two different strategies, overexpression of an antisense PKR transcript or a dominant negative PKR mutant gene. Both types of PKR-deficient cells were more permissive for viral replication than the control U-937 cells. As the result of PKR loss, they also showed impaired induction of IFN-α and IFN-β genes in response to several inducers-specifically, encephalomyocarditis virus, lipopolysaccharide, and phorbol 12-myristate 13-acetate. Interestingly, while IFN-α induction by dsRNA was impaired in PKR-deficient cells, IFN-β induction remained intact. Loss of PKR function also resulted in decreased antiviral activity as elicited by IFN-α and, to a greater extent, by IFN- γ. These results implicate PKR in the regulation of several antiviral activities.en_US
dc.languageengen_US
dc.publisherNational Academy of Sciences. The Journal's web site is located at http://www.pnas.orgen_US
dc.relation.ispartofProceedings of the National Academy of Sciences of the United States of Americaen_US
dc.subject.meshBase Sequenceen_US
dc.subject.meshDna, Antisenseen_US
dc.subject.meshEncephalomyocarditis Virus - Drug Effects - Growth & Developmenten_US
dc.subject.meshGene Expression Regulationen_US
dc.subject.meshHumansen_US
dc.subject.meshInterferon-Alpha - Biosynthesis - Pharmacologyen_US
dc.subject.meshInterferon-Beta - Biosynthesis - Pharmacologyen_US
dc.subject.meshInterferons - Biosynthesis - Pharmacologyen_US
dc.subject.meshMolecular Sequence Dataen_US
dc.subject.meshMonocytes - Enzymology - Metabolismen_US
dc.subject.meshMutationen_US
dc.subject.meshProtein-Serine-Threonine Kinases - Biosynthesis - Deficiency - Geneticsen_US
dc.subject.meshSuppression, Geneticen_US
dc.subject.meshVirus Replication - Drug Effectsen_US
dc.subject.meshEif-2 Kinaseen_US
dc.titleInvolvement of the double-stranded-RNA-dependent kinase PKR in interferon expression and interferon-mediated antiviral activityen_US
dc.typeArticleen_US
dc.identifier.emailLau, AS:asylau@hku.hken_US
dc.identifier.authorityLau, AS=rp00474en_US
dc.description.naturelink_to_subscribed_fulltexten_US
dc.identifier.doi10.1073/pnas.92.19.8841en_US
dc.identifier.pmid7568028-
dc.identifier.scopuseid_2-s2.0-0029051672en_US
dc.identifier.volume92en_US
dc.identifier.issue19en_US
dc.identifier.spage8841en_US
dc.identifier.epage8845en_US
dc.identifier.isiWOS:A1995RU75900063-
dc.publisher.placeUnited Statesen_US
dc.identifier.scopusauthoridDer, SD=7003963925en_US
dc.identifier.scopusauthoridLau, AS=7202626202en_US

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