Latent membrane protein 1 of Epstein-Barr virus activates the hTERT promoter and enhances telomerase activity in B lymphocytes

Terrin, Liliana, Dal Col, Jessica, Rampazzo, Enrica, Zancai, Paola, Pedrotti, Moreno, Ammirabile, Grazia, Bergamin, Stefano, Rizzo, Silvana, Dolcetti, Riccardo and De Rossi, Anita (2008) Latent membrane protein 1 of Epstein-Barr virus activates the hTERT promoter and enhances telomerase activity in B lymphocytes. Journal of Virology, 82 20: 10175-10187. doi:10.1128/JVI.00321-08

Attached Files (Some files may be inaccessible until you login with your UQ eSpace credentials)
Name Description MIMEType Size Downloads
UQ374381_OA.pdf Full text (open access) application/pdf 1.88MB 0

Author Terrin, Liliana
Dal Col, Jessica
Rampazzo, Enrica
Zancai, Paola
Pedrotti, Moreno
Ammirabile, Grazia
Bergamin, Stefano
Rizzo, Silvana
Dolcetti, Riccardo
De Rossi, Anita
Title Latent membrane protein 1 of Epstein-Barr virus activates the hTERT promoter and enhances telomerase activity in B lymphocytes
Journal name Journal of Virology   Check publisher's open access policy
ISSN 0022-538X
1098-5514
Publication date 2008-10
Sub-type Article (original research)
DOI 10.1128/JVI.00321-08
Open Access Status File (Publisher version)
Volume 82
Issue 20
Start page 10175
End page 10187
Total pages 13
Place of publication Washington, DC, United States
Publisher American Society for Microbiology
Language eng
Formatted abstract
Transformation of primary B lymphocytes by Epstein-Barr virus requires the establishment of a strictly latent infection, the expression of several latent viral proteins, and sustained telomerase activity. Our previous findings indicated that induction of hTERT, the rate-limiting catalytic unit of the telomerase complex, was associated with the expression of the viral latent membrane protein 1 (LMP1). In the present study, we demonstrate that ectopic expression of LMP1 in BJAB and Ramos B cells resulted in an increase of hTERT transcripts, thus suggesting that LMP1 acts at the transcriptional level. This was confirmed by transient expression of a luciferase reporter plasmid containing the hTERT promoter cotransfected with an LMP1-expressing vector or transfected into B cells in which LMP1 expression was inducible. Consistently, silencing of LMP1 by small interfering RNA resulted in a reduction of hTERT transcripts. We also provide evidence indicating that LMP1-induced hTERT activation is independently mediated by NF-κB and by mitogen-activated protein kinase and extracellular signal-regulated kinase 1/2 pathways, whereas CD40, Akt, and mTOR signaling has no involvement. Moreover, our results do not support a role for c-Myc in mediating these effects on hTERT, since ectopic expression of LMP1 did not upregulate c-Myc and silencing of this oncogene or E box mutagenesis failed to inhibit LMP1-induced hTERT activation. These findings indicate that LMP1 simultaneously modulates multiple signal transduction pathways in B cells to transactivate the hTERT promoter and enhance telomerase activity, thus confirming the pleiotropic nature of this viral oncoprotein. 
Q-Index Code C1
Q-Index Status Provisional Code
Institutional Status Non-UQ

Document type: Journal Article
Sub-type: Article (original research)
Collection: UQ Diamantina Institute Publications
 
Versions
Version Filter Type
Citation counts: TR Web of Science Citation Count  Cited 29 times in Thomson Reuters Web of Science Article | Citations
Scopus Citation Count Cited 31 times in Scopus Article | Citations
Google Scholar Search Google Scholar
Created: Fri, 27 Nov 2015, 19:54:23 EST by System User on behalf of Learning and Research Services (UQ Library)