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Article: The Epstein-Barr virus latency BamHI-Q promoter is positively regulated by STATs and Zta interference with JAK/STAT activation leads to loss of BamHI-Q promoter activity

TitleThe Epstein-Barr virus latency BamHI-Q promoter is positively regulated by STATs and Zta interference with JAK/STAT activation leads to loss of BamHI-Q promoter activity
Authors
Issue Date1999
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, 1999, v. 96 n. 16, p. 9339-9344 How to Cite?
AbstractIn Epstein-Barr virus (EBV)-associated tumors in nonimmunocompromised patients, EBV gene expression is highly restricted. EBV-encoded nuclear antigen (EBNA)-1 is expressed, whereas the immunogenic and proliferative EBNAs are not. This pattern of EBNA expression is generated by usage of the BamHI-Q promoter (Qp). We have determined that the JAK/STAT pathway positively regulates Qp activity. In transient-transfection assays, a Qp-CAT reporter was activated by cotransfected JAK-1 and by treatment of cells with the cytokine IL-6. The ability of Qp to bind signal transducer and activator of transcription (STAT) proteins was directly demonstrated by electrophoretic mobility-shift assay, and mutation of potential STAT-binding sites reduced Qp responsiveness to Janus kinase (JAK)-1. Consistent with a role for STATs in Qp function, Qp using Burkitt's lymphoma Rael cells and cultured nasopharyngeal carcinoma (NPC) cells contained nuclear STAT protein. We investigated whether the inability to maintain EBV-positive NPC cell lines in culture was related to Qp activity. Passaging of the NPC cell line HK666 led to activation of expression of BZLF1, which encodes Zta and loss of Qp function. Transient expression assays linked Zta expression to the down-regulation of Qp. Cotransfection of Zta reduced Qp activity in reporter assays. This negative regulation required Zta DNA-binding activity. We provide evidence that Zta up-regulation of p53 leads to p53-mediated interference with JAK/STAT activation of Qp. The data imply that JAK/STAT signaling has a role in EBV-associated malignancies.
Persistent Identifierhttp://hdl.handle.net/10722/157304
ISSN
2015 Impact Factor: 9.423
2015 SCImago Journal Rankings: 6.883
ISI Accession Number ID
References

 

DC FieldValueLanguage
dc.contributor.authorChen, Hen_US
dc.contributor.authorLee, JMen_US
dc.contributor.authorWang, Yen_US
dc.contributor.authorHuang, DPen_US
dc.contributor.authorAmbinder, RFen_US
dc.contributor.authorHayward, SDen_US
dc.date.accessioned2012-08-08T08:48:47Z-
dc.date.available2012-08-08T08:48:47Z-
dc.date.issued1999en_US
dc.identifier.citationProceedings Of The National Academy Of Sciences Of The United States Of America, 1999, v. 96 n. 16, p. 9339-9344en_US
dc.identifier.issn0027-8424en_US
dc.identifier.urihttp://hdl.handle.net/10722/157304-
dc.description.abstractIn Epstein-Barr virus (EBV)-associated tumors in nonimmunocompromised patients, EBV gene expression is highly restricted. EBV-encoded nuclear antigen (EBNA)-1 is expressed, whereas the immunogenic and proliferative EBNAs are not. This pattern of EBNA expression is generated by usage of the BamHI-Q promoter (Qp). We have determined that the JAK/STAT pathway positively regulates Qp activity. In transient-transfection assays, a Qp-CAT reporter was activated by cotransfected JAK-1 and by treatment of cells with the cytokine IL-6. The ability of Qp to bind signal transducer and activator of transcription (STAT) proteins was directly demonstrated by electrophoretic mobility-shift assay, and mutation of potential STAT-binding sites reduced Qp responsiveness to Janus kinase (JAK)-1. Consistent with a role for STATs in Qp function, Qp using Burkitt's lymphoma Rael cells and cultured nasopharyngeal carcinoma (NPC) cells contained nuclear STAT protein. We investigated whether the inability to maintain EBV-positive NPC cell lines in culture was related to Qp activity. Passaging of the NPC cell line HK666 led to activation of expression of BZLF1, which encodes Zta and loss of Qp function. Transient expression assays linked Zta expression to the down-regulation of Qp. Cotransfection of Zta reduced Qp activity in reporter assays. This negative regulation required Zta DNA-binding activity. We provide evidence that Zta up-regulation of p53 leads to p53-mediated interference with JAK/STAT activation of Qp. The data imply that JAK/STAT signaling has a role in EBV-associated malignancies.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.meshB-Lymphocytesen_US
dc.subject.meshBase Sequenceen_US
dc.subject.meshBurkitt Lymphomaen_US
dc.subject.meshCell Lineen_US
dc.subject.meshChloramphenicol O-Acetyltransferase - Geneticsen_US
dc.subject.meshDna-Binding Proteins - Metabolismen_US
dc.subject.meshEpstein-Barr Virus Nuclear Antigens - Biosynthesis - Geneticsen_US
dc.subject.meshGene Expression Regulation, Viralen_US
dc.subject.meshHela Cellsen_US
dc.subject.meshHerpesvirus 4, Human - Geneticsen_US
dc.subject.meshHumansen_US
dc.subject.meshMolecular Sequence Dataen_US
dc.subject.meshMutagenesis, Site-Directeden_US
dc.subject.meshNasopharyngeal Neoplasmsen_US
dc.subject.meshPromoter Regions, Geneticen_US
dc.subject.meshProtein-Tyrosine Kinases - Metabolismen_US
dc.subject.meshRecombinant Fusion Proteins - Biosynthesisen_US
dc.subject.meshStat1 Transcription Factoren_US
dc.subject.meshStat4 Transcription Factoren_US
dc.subject.meshSignal Transductionen_US
dc.subject.meshTrans-Activators - Metabolismen_US
dc.subject.meshTransfectionen_US
dc.subject.meshTumor Cells, Cultureden_US
dc.subject.meshVirus Latencyen_US
dc.titleThe Epstein-Barr virus latency BamHI-Q promoter is positively regulated by STATs and Zta interference with JAK/STAT activation leads to loss of BamHI-Q promoter activityen_US
dc.typeArticleen_US
dc.identifier.emailChen, H:hlchen@hkucc.hku.hken_US
dc.identifier.authorityChen, H=rp00383en_US
dc.description.naturelink_to_subscribed_fulltexten_US
dc.identifier.pmid10430944-
dc.identifier.scopuseid_2-s2.0-0033529876en_US
dc.relation.referenceshttp://www.scopus.com/mlt/select.url?eid=2-s2.0-0033529876&selection=ref&src=s&origin=recordpageen_US
dc.identifier.volume96en_US
dc.identifier.issue16en_US
dc.identifier.spage9339en_US
dc.identifier.epage9344en_US
dc.identifier.isiWOS:000081835500102-
dc.publisher.placeUnited Statesen_US
dc.identifier.scopusauthoridChen, H=26643315400en_US
dc.identifier.scopusauthoridLee, JM=24177059700en_US
dc.identifier.scopusauthoridWang, Y=37074939100en_US
dc.identifier.scopusauthoridHuang, DP=7403891486en_US
dc.identifier.scopusauthoridAmbinder, RF=7005598325en_US
dc.identifier.scopusauthoridHayward, SD=7102776214en_US

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