Epstein-Barr virus latent membrane 2A (LMP2A) down-regulates telomerase reverse transcriptase (hTERT) in epithelial cell lines.
The latent membrane protein (LMP) 2A, one of the membrane-spanning polypeptides encoded by the Epstein-Barr virus (EBV), has been implicated in the maintenance of viral latency and appears to function in part by inhibiting B-cell receptor (BCR) signaling through its ITAM motifs. It has also been suggested that LMP2A is involved in tumorigenesis mediated by EBV. In our study, we determined regulatory effects of LMP2A on the telomerase reverse transcriptase (hTERT) expression. We observed a significant and constant reduction of hTERT mRNA accompanied by decreased telomerase activity in epithelial cells expressing LMP2A. It was further shown that LMP2A inhibited the hTERT promoter activity in transient transfections of both B cells and epithelial cells, and that the ITAM motif was required for this inhibition. Thus LMP2A expression leads to the transcriptional repression of the hTERT gene through specific pathways, which may thereby contribute to the control of EBV-latency.
Chen
Fu
F
Microbiology and Tumor Biology Centre (MTC), Karolinska Institute, Stockholm, Sweden.
Liu
Cheng
C
Lindvall
Charlotta
C
Xu
Dawei
D
Ernberg
Ingemar
I
D002277:Carcinoma / Q000473:pathology; D004268:DNA-Binding Proteins; D015536:Down-Regulation; D004847:Epithelial Cells; D005786:Gene Expression Regulation; D004854:Herpesvirus 4, Human / Q000502:physiology*; D006801:Humans; D012333:RNA, Messenger / Q000096:biosynthesis; D019098:Telomerase / Q000096:biosynthesis*; D014158:Transcription, Genetic; D014407:Tumor Cells, Cultured; D001749:Urinary Bladder Neoplasms / Q000473:pathology; D014763:Viral Matrix Proteins / Q000494:pharmacology*; D017735:Virus Latency
D004268:DNA-Binding Proteins; C037662:EBV-associated membrane antigen, Epstein-Barr virus; D012333:RNA, Messenger; D014763:Viral Matrix Proteins; D019098:Telomerase