Telomerase activation by Epstein-Barr virus latent membrane protein 1 is associated with c-Myc expression in human nasopharyngeal epithelial cells.
Latent membrane protein 1 (LMP1), one of the oncoproteins encoded by Epstein-Barr virus is sufficient for the development of nasopharyngeal carcinoma in vivo and nasopharyngeal epithelial cellular immortalization in vitro. It has also been shown to increase the telomerase activity in primary human nasopharyngeal epithelial cells by an unknown mechanism. We reported here that LMP1 could increase telomerase activity in coordination with LMP1-induced c-Myc expression in LMP1-transfected primary human nasopharyngeal epithelial cells or in a dual-stable LMP1 integrated nasopharyngeal carcinoma cell line with Tet-on regulatory system, named Tet-on-LMP1 HNE2 by PCR-ELISA analysis and reporter gene assay. Blocking of LMP1 expression decreased telomerase activity and c-myc transactivation. Mutagenesis of Myc-responsive E-box elements in the minimal core of hTERT promoter could inhibit the hTERT expression induced by LMP1. Moreover, blocking of c-myc transactivation could further decrease LMP1-mediated hTERT expression. It has been suggested that LMP1 can be used to aid myc control telomerase. In addition, we also found that C-terminus of LMP1, including CTAR1 and CTAR2 domains participated in telomerase activation. Together, these findings suggested that LMP1 activated telomerase via c-myc.
Yang
J
J
Dept of Pathology and laboratory Medicine, University of South Carolina, Charleston, USA.
Deng
X
X
Deng
L
L
Gu
H
H
Fan
W
W
Cao
Y
Y
D015153:Blotting, Western; D002460:Cell Line; D045744:Cell Line, Tumor; D002471:Cell Transformation, Neoplastic; D002478:Cells, Cultured; D018076:DNA, Complementary / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D004789:Enzyme Activation; D004797:Enzyme-Linked Immunosorbent Assay; D004847:Epithelial Cells / Q000378:metabolism*; D017930:Genes, Reporter; D006367:HeLa Cells; D004854:Herpesvirus 4, Human / Q000378:metabolism*; D006801:Humans; D007150:Immunohistochemistry; D016296:Mutagenesis; D009303:Nasopharyngeal Neoplasms / Q000378:metabolism*; D009305:Nasopharynx / Q000378:metabolism; D010957:Plasmids / Q000378:metabolism; D016133:Polymerase Chain Reaction; D011401:Promoter Regions, Genetic; D011485:Protein Binding; D017434:Protein Structure, Tertiary; D016271:Proto-Oncogene Proteins c-myc / Q000096:biosynthesis*; D015398:Signal Transduction; D019098:Telomerase / Q000378:metabolism*; D015533:Transcriptional Activation; D014162:Transfection; D014763:Viral Matrix Proteins / Q000378:metabolism*
D018076:DNA, Complementary; C037662:EBV-associated membrane antigen, Epstein-Barr virus; D016271:Proto-Oncogene Proteins c-myc; D014763:Viral Matrix Proteins; D019098:Telomerase