Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
2
pubmed:dateCreated
2010-4-5
pubmed:abstractText
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-kappaB 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-kappaB activation and histone H3 Ser 10 phosphorylation.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
http://linkedlifedata.com/resource/pubmed/chemical/EBV-associated membrane antigen..., http://linkedlifedata.com/resource/pubmed/chemical/Eukaryotic Initiation Factor-2B, http://linkedlifedata.com/resource/pubmed/chemical/Histones, http://linkedlifedata.com/resource/pubmed/chemical/IL10 protein, human, http://linkedlifedata.com/resource/pubmed/chemical/IL6 protein, human, http://linkedlifedata.com/resource/pubmed/chemical/Interleukin-10, http://linkedlifedata.com/resource/pubmed/chemical/Interleukin-6, http://linkedlifedata.com/resource/pubmed/chemical/NF-kappa B, http://linkedlifedata.com/resource/pubmed/chemical/Protein Kinase Inhibitors, http://linkedlifedata.com/resource/pubmed/chemical/Viral Matrix Proteins, http://linkedlifedata.com/resource/pubmed/chemical/eIF-2 Kinase, http://linkedlifedata.com/resource/pubmed/chemical/p38 Mitogen-Activated Protein...
pubmed:status
MEDLINE
pubmed:month
May
pubmed:issn
1096-0023
pubmed:author
pubmed:copyrightInfo
Copyright (c) 2010 Elsevier Ltd. All rights reserved.
pubmed:issnType
Electronic
pubmed:volume
50
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
210-9
pubmed:meshHeading
pubmed:year
2010
pubmed:articleTitle
A role for protein kinase PKR in the mediation of Epstein-Barr virus latent membrane protein-1-induced IL-6 and IL-10 expression.
pubmed:affiliation
Cytokine Biology Group, Department of Paediatrics and Adolescent Medicine, The University of Hong Kong, Pokfulam, Hong Kong SAR, China.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't