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Article: A role for protein kinase PKR in the mediation of Epstein-Barr virus latent membrane protein-1-induced IL-6 and IL-10 expression

TitleA role for protein kinase PKR in the mediation of Epstein-Barr virus latent membrane protein-1-induced IL-6 and IL-10 expression
Authors
KeywordsCytokine
EBV
Kinase
LMP1
PKR
Issue Date2010
PublisherAcademic Press. The Journal's web site is located at http://www.elsevier.com/locate/cytokine
Citation
Cytokine, 2010, v. 50 n. 2, p. 210-219 How to Cite?
AbstractExpression of Epstein-Barr virus-encoded oncogenic latent membrane protein 1 (LMP1) has been substantially associated with tumorigenic transformation in the virus-infected cells. The pathogenic complexity of LMP1 is partly due to the cytokine dysregulation including IL-6 and IL-10 in perturbing the host immune responses. Here we have identified an important signaling event mediated by a dsRNA-dependent serine/threonine protein kinase, PKR, in regulating LMP1-induced IL-6 and IL-10 expression. We first demonstrated that PKR plays a significant role in mediating LMP1-induced cytokine expression by using a PKR inhibitor 2-aminopurine, and the specific role of PKR involved was confirmed by the use of siRNA oligos targeting PKR and/or a dominant-negative PKR mutant. We next revealed that PKR activity mediates LMP1-enhanced NF-κB nuclear translocation resulting in cytokine induction. We further demonstrated at the chromatin level that LMP1 can significantly elevate the phosphorylation of histone H3 on serine 10 (Ser 10), and the process was dependent on PKR activity. Our findings thus suggest that PKR plays an important role in mediating the cytokine gene expression induced by LMP1 through NF-κB activation and histone H3 Ser 10 phosphorylation. © 2010 Elsevier Ltd.
Persistent Identifierhttp://hdl.handle.net/10722/127597
ISSN
2014 Impact Factor: 2.664
2014 SCImago Journal Rankings: 1.078
ISI Accession Number ID
Funding AgencyGrant Number
Hong Kong Research Grants CouncilHKU 7685/07M
HKU 7685/09M
HKU Clinical Oncology Research Fund
Funding Information:

This work was supported by grants to A.S. Lau from Hong Kong Research Grants Council (HKU 7685/07M and HKU 7685/09M), and to A.S. Lau and D.T.T. Chua from HKU Clinical Oncology Research Fund.

References

 

DC FieldValueLanguage
dc.contributor.authorLin, SSen_HK
dc.contributor.authorLee, DCWen_HK
dc.contributor.authorLaw, AHYen_HK
dc.contributor.authorFang, JWen_HK
dc.contributor.authorChua, DTTen_HK
dc.contributor.authorLau, ASYen_HK
dc.date.accessioned2010-10-31T13:34:46Z-
dc.date.available2010-10-31T13:34:46Z-
dc.date.issued2010en_HK
dc.identifier.citationCytokine, 2010, v. 50 n. 2, p. 210-219en_HK
dc.identifier.issn1043-4666en_HK
dc.identifier.urihttp://hdl.handle.net/10722/127597-
dc.description.abstractExpression of Epstein-Barr virus-encoded oncogenic latent membrane protein 1 (LMP1) has been substantially associated with tumorigenic transformation in the virus-infected cells. The pathogenic complexity of LMP1 is partly due to the cytokine dysregulation including IL-6 and IL-10 in perturbing the host immune responses. Here we have identified an important signaling event mediated by a dsRNA-dependent serine/threonine protein kinase, PKR, in regulating LMP1-induced IL-6 and IL-10 expression. We first demonstrated that PKR plays a significant role in mediating LMP1-induced cytokine expression by using a PKR inhibitor 2-aminopurine, and the specific role of PKR involved was confirmed by the use of siRNA oligos targeting PKR and/or a dominant-negative PKR mutant. We next revealed that PKR activity mediates LMP1-enhanced NF-κB nuclear translocation resulting in cytokine induction. We further demonstrated at the chromatin level that LMP1 can significantly elevate the phosphorylation of histone H3 on serine 10 (Ser 10), and the process was dependent on PKR activity. Our findings thus suggest that PKR plays an important role in mediating the cytokine gene expression induced by LMP1 through NF-κB activation and histone H3 Ser 10 phosphorylation. © 2010 Elsevier Ltd.en_HK
dc.languageengen_HK
dc.publisherAcademic Press. The Journal's web site is located at http://www.elsevier.com/locate/cytokineen_HK
dc.relation.ispartofCytokineen_HK
dc.subjectCytokineen_HK
dc.subjectEBVen_HK
dc.subjectKinaseen_HK
dc.subjectLMP1en_HK
dc.subjectPKRen_HK
dc.subject.meshCell Line-
dc.subject.meshInterleukin-10 - genetics - metabolism-
dc.subject.meshInterleukin-6 - genetics - metabolism-
dc.subject.meshViral Matrix Proteins - metabolism-
dc.subject.mesheIF-2 Kinase - metabolism-
dc.titleA role for protein kinase PKR in the mediation of Epstein-Barr virus latent membrane protein-1-induced IL-6 and IL-10 expressionen_HK
dc.typeArticleen_HK
dc.identifier.openurlhttp://library.hku.hk:4550/resserv?sid=HKU:IR&issn=1043-4666&volume=50&issue=2&spage=210&epage=219&date=2010&atitle=A+role+for+protein+kinase+PKR+in+the+medication+of+Epstien-Barr+virus+latent+membrane+protein-1-induced+IL-6+and+IL-10+expressionen_HK
dc.identifier.emailChua, DTT: dttchua@hkucc.hku.hken_HK
dc.identifier.emailLau, ASY: asylau@hku.hken_HK
dc.identifier.authorityChua, DTT=rp00415en_HK
dc.identifier.authorityLau, ASY=rp00474en_HK
dc.description.naturelink_to_subscribed_fulltext-
dc.identifier.doi10.1016/j.cyto.2010.01.008en_HK
dc.identifier.pmid20171114-
dc.identifier.scopuseid_2-s2.0-77950864152en_HK
dc.identifier.hkuros171735en_HK
dc.relation.referenceshttp://www.scopus.com/mlt/select.url?eid=2-s2.0-77950864152&selection=ref&src=s&origin=recordpageen_HK
dc.identifier.volume50en_HK
dc.identifier.issue2en_HK
dc.identifier.spage210en_HK
dc.identifier.epage219en_HK
dc.identifier.isiWOS:000277496700018-
dc.publisher.placeUnited Kingdomen_HK
dc.identifier.scopusauthoridLin, SS=37099455700en_HK
dc.identifier.scopusauthoridLee, DCW=15751156000en_HK
dc.identifier.scopusauthoridLaw, AHY=8692488400en_HK
dc.identifier.scopusauthoridFang, JW=36150695100en_HK
dc.identifier.scopusauthoridChua, DTT=7006773480en_HK
dc.identifier.scopusauthoridLau, ASY=7202626202en_HK
dc.identifier.citeulike6869123-

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