Epstein-Barr virus latent membrane protein 1 induces CD69 expression through activation of nuclear factor-κB
Epstein-Barr virus latent membrane protein 1 induces CD69 expression through activation of nuclear factor-κB
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DOI：
10.3892/ijo.2013.1871
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发表时间：
2013-05-01
影响因子：
5.2
通讯作者：
Mori, Naoki
中科院分区：
文献类型：
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作者：
Ishikawa, Chie;Mori, Naoki
EB病毒潜伏膜蛋白1（LMP-1）促进肿瘤发生。在这里，我们报告说，LMP-1激活免疫调节分子CD 69基因转录通过核因子-κ B（NF-κ B）依赖性途径。在表达LMP-1的EBV永生化人B细胞系和EBV阳性伯基特淋巴瘤细胞系中，CD 69表达上调。LMP-1表达在转录水平上增加了CD 69表达。CD 69启动子受NF-κ B的LMP-1活化通过羧基末端活化区1和2调节。启动子缺失分析表明，两个NF-κ B结合位点是激活CD 69启动子所必需的。电泳迁移率变动分析表明，LMP-1激活CD 69启动子中的两个NF-κ B结合位点。这是LMP-1调控CD 69表达的首次报道，因此，这一新的发现可能代表了EBV癌蛋白LMP-1及其在EBV相关疾病发展中的关键作用之间的重要联系。
Latent membrane protein-1 (LMP-1) of Epstein-Barr virus (EBV) promotes tumorigenesis. Here, we report that LMP-1 activates the immunoregulatory molecule CD69 gene transcription through a nuclear factor-kappa B (NF-kappa B)-dependent pathway. CD69 expression was upregulated in LMP-1-expressing EBV-immortalized human B-cell lines and an EBV-positive Burkitt's lymphoma cell line. LMP-1 expression increased CD69 expression at the transcriptional level. CD69 promoter was regulated by LMP-1 activation of NF-kappa B via the carboxy-terminal activation region 1 and 2. Promoter deletion analysis indicated that two NF-kappa B binding sites are necessary for activation of the CD69 promoter. Electrophoretic mobility shift analysis demonstrated that LMP-1 activates both NF-kappa B binding sites in the CD69 promoter. This is the first report of the regulation of CD69 expression by LMP-1, and this novel finding may, thus, represent an important link between the EBV oncoprotein LMP-1 and its critical role in the development of EBV-associated diseases.