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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
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TitleA role for protein kinase PKR in the mediation of Epstein-Barr virus latent membrane protein-1-induced IL-6 and IL-10 expression
 
AuthorsLin, SS2
Lee, DCW2
Law, AHY2
Fang, JW2
Chua, DTT1
Lau, ASY2
 
KeywordsCytokine
EBV
Kinase
LMP1
PKR
 
Issue Date2010
 
PublisherAcademic Press. The Journal's web site is located at http://www.elsevier.com/locate/cytokine
 
CitationCytokine, 2010, v. 50 n. 2, p. 210-219 [How to Cite?]
DOI: http://dx.doi.org/10.1016/j.cyto.2010.01.008
 
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.
 
ISSN1043-4666
2013 Impact Factor: 2.874
 
DOIhttp://dx.doi.org/10.1016/j.cyto.2010.01.008
 
ISI Accession Number IDWOS:000277496700018
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.

 
ReferencesReferences in Scopus
 
DC FieldValue
dc.contributor.authorLin, SS
 
dc.contributor.authorLee, DCW
 
dc.contributor.authorLaw, AHY
 
dc.contributor.authorFang, JW
 
dc.contributor.authorChua, DTT
 
dc.contributor.authorLau, ASY
 
dc.date.accessioned2010-10-31T13:34:46Z
 
dc.date.available2010-10-31T13:34:46Z
 
dc.date.issued2010
 
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.
 
dc.description.naturelink_to_subscribed_fulltext
 
dc.identifier.citationCytokine, 2010, v. 50 n. 2, p. 210-219 [How to Cite?]
DOI: http://dx.doi.org/10.1016/j.cyto.2010.01.008
 
dc.identifier.citeulike6869123
 
dc.identifier.doihttp://dx.doi.org/10.1016/j.cyto.2010.01.008
 
dc.identifier.epage219
 
dc.identifier.hkuros171735
 
dc.identifier.isiWOS:000277496700018
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.

 
dc.identifier.issn1043-4666
2013 Impact Factor: 2.874
 
dc.identifier.issue2
 
dc.identifier.openurl
 
dc.identifier.pmid20171114
 
dc.identifier.scopuseid_2-s2.0-77950864152
 
dc.identifier.spage210
 
dc.identifier.urihttp://hdl.handle.net/10722/127597
 
dc.identifier.volume50
 
dc.languageeng
 
dc.publisherAcademic Press. The Journal's web site is located at http://www.elsevier.com/locate/cytokine
 
dc.publisher.placeUnited Kingdom
 
dc.relation.ispartofCytokine
 
dc.relation.referencesReferences in Scopus
 
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.subjectCytokine
 
dc.subjectEBV
 
dc.subjectKinase
 
dc.subjectLMP1
 
dc.subjectPKR
 
dc.titleA role for protein kinase PKR in the mediation of Epstein-Barr virus latent membrane protein-1-induced IL-6 and IL-10 expression
 
dc.typeArticle
 
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<description.abstract>Expression 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-&#954;B 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-&#954;B activation and histone H3 Ser 10 phosphorylation. &#169; 2010 Elsevier Ltd.</description.abstract>
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Author Affiliations
  1. The University of Hong Kong Li Ka Shing Faculty of Medicine
  2. The University of Hong Kong