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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- Publisher Website: 10.1016/j.cyto.2010.01.008
- Scopus: eid_2-s2.0-77950864152
- PMID: 20171114
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| Title | A role for protein kinase PKR in the mediation of Epstein-Barr virus latent membrane protein-1-induced IL-6 and IL-10 expression | ||||||
|---|---|---|---|---|---|---|---|
| Authors | Lin, SS2 Lee, DCW2 Law, AHY2 Fang, JW2 Chua, DTT1 Lau, ASY2 | ||||||
| Keywords | Cytokine EBV Kinase LMP1 PKR | ||||||
| Issue Date | 2010 | ||||||
| Publisher | Academic 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?] DOI: http://dx.doi.org/10.1016/j.cyto.2010.01.008 | ||||||
| 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-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. | ||||||
| ISSN | 1043-4666 2011 Impact Factor: 3.019 2011 SCImago Journal Rankings: 0.410 | ||||||
| DOI | http://dx.doi.org/10.1016/j.cyto.2010.01.008 | ||||||
| ISI Accession Number ID | WOS:000277496700018
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 | References in Scopus |
| dc.contributor.author | Lin, SS | ||||||
|---|---|---|---|---|---|---|---|
| dc.contributor.author | Lee, DCW | ||||||
| dc.contributor.author | Law, AHY | ||||||
| dc.contributor.author | Fang, JW | ||||||
| dc.contributor.author | Chua, DTT | ||||||
| dc.contributor.author | Lau, ASY | ||||||
| dc.date.accessioned | 2010-10-31T13:34:46Z | ||||||
| dc.date.available | 2010-10-31T13:34:46Z | ||||||
| dc.date.issued | 2010 | ||||||
| dc.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-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.nature | Link_to_subscribed_fulltext | ||||||
| dc.identifier.citation | Cytokine, 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.citeulike | 6869123 | ||||||
| dc.identifier.doi | http://dx.doi.org/10.1016/j.cyto.2010.01.008 | ||||||
| dc.identifier.epage | 219 | ||||||
| dc.identifier.hkuros | 171735 | ||||||
| dc.identifier.isi | WOS:000277496700018
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.issn | 1043-4666 2011 Impact Factor: 3.019 2011 SCImago Journal Rankings: 0.410 | ||||||
| dc.identifier.issue | 2 | ||||||
| dc.identifier.openurl | | ||||||
| dc.identifier.pmid | 20171114 | ||||||
| dc.identifier.scopus | eid_2-s2.0-77950864152 | ||||||
| dc.identifier.spage | 210 | ||||||
| dc.identifier.uri | http://hdl.handle.net/10722/127597 | ||||||
| dc.identifier.volume | 50 | ||||||
| dc.language | eng | ||||||
| dc.publisher | Academic Press. The Journal's web site is located at http://www.elsevier.com/locate/cytokine | ||||||
| dc.publisher.place | United Kingdom | ||||||
| dc.relation.ispartof | Cytokine | ||||||
| dc.relation.references | References in Scopus | ||||||
| dc.subject.mesh | Cell Line | ||||||
| dc.subject.mesh | Interleukin-10 - genetics - metabolism | ||||||
| dc.subject.mesh | Interleukin-6 - genetics - metabolism | ||||||
| dc.subject.mesh | Viral Matrix Proteins - metabolism | ||||||
| dc.subject.mesh | eIF-2 Kinase - metabolism | ||||||
| dc.subject | Cytokine | ||||||
| dc.subject | EBV | ||||||
| dc.subject | Kinase | ||||||
| dc.subject | LMP1 | ||||||
| dc.subject | PKR | ||||||
| dc.title | A role for protein kinase PKR in the mediation of Epstein-Barr virus latent membrane protein-1-induced IL-6 and IL-10 expression | ||||||
| dc.type | Article |
Author Affiliations
- The University of Hong Kong Li Ka Shing Faculty of Medicine
- The University of Hong Kong