Epstein-Barr virus latent membrane 2A (LMP2A) down-regulates telomerase reverse transcriptase (hTERT) in epithelial cell lines
Epstein-Barr virus latent membrane 2A (LMP2A) down-regulates telomerase reverse transcriptase (hTERT) in epithelial cell lines
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DOI：
10.1002/ijc.20594
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发表时间：
2005-01-10
影响因子：
6.4
通讯作者：
Ernberg, I
中科院分区：
文献类型：
--
作者：
Chen, F;Liu, C;Ernberg, I
潜伏膜蛋白（LMP）2A是由EB病毒（EBV）编码的跨膜多肽之一，其与病毒潜伏期的维持有关，并且似乎部分地通过其ITAM基序抑制B细胞受体（BCR）信号传导而起作用。也有人认为LMP2A参与EBV介导的肿瘤发生。在我们的研究中，我们确定了LMP2A对端粒酶逆转录酶（hTERT）表达的调节作用。我们观察到一个显着的和不断减少的hTERTmRNA伴随着降低端粒酶活性的上皮细胞表达LMP2A。进一步显示，LMP 2A在B细胞和上皮细胞的瞬时转染中抑制hTERT启动子活性，并且该抑制需要ITAM基序。因此，LMP2A表达通过特定途径导致hTERT基因的转录抑制，从而可能有助于控制EBV潜伏期。
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.