Epstein-Barr virus latent membrane protein 1 (LMP1) upregulates Id1 expression in nasopharyngeal epithelial cells
Epstein-Barr virus latent membrane protein 1 (LMP1) upregulates Id1 expression in nasopharyngeal epithelial cells
复制标题
DOI：
10.1038/sj.onc.1207580
复制
发表时间：
2004-05-27
期刊：
影响因子：
8
通讯作者：
Tsao, SW
中科院分区：
文献类型：
--
作者：
Li, HM;Zhuang, ZH;Tsao, SW
鼻咽癌与EB病毒感染密切相关。EBV编码的LMP 1具有细胞转化特性。它抑制细胞衰老并增强各种细胞类型的细胞存活。LMP 1表达的许多下游事件通过其激活NF-κ B的能力介导。在这项研究中，我们报告了LMP 1诱导鼻咽上皮细胞（NP 69）和人胚肾细胞（HEK 293）中Id 1表达的新功能。Id 1是一种碱性螺旋-环-螺旋（bHLH）蛋白，是p16（INK 4a）的负转录调节因子。Id 1的表达促进细胞永生化并刺激细胞增殖。结合细胞信号传导的特异性化学抑制剂和遗传抑制剂，我们发现LMP 1对Id 1的诱导依赖于其羧基末端区域的NF-κ B激活结构域CTAR 1和CTAR 2。LMP 1诱导Id 1可能促进EBV感染的癌前鼻咽上皮细胞的克隆性扩增，并可能促进其恶性转化。
Nasopharyngeal carcinoma is closely associated with Epstein-Barr virus (EBV) infection. The EBV-encoded LMP1 has cell transformation property. It suppresses cellular senescence and enhances cell survival in various cell types. Many of the downstream events of LMP1 expression are mediated through its ability to activate NF-kappaB. In this study, we report a novel function of LMP1 to induce Id1 expression in nasopharyngeal epithelial cells (NP69) and human embryonal kidney cells (HEK293). The Id1 is a basic helix-loop-helix (bHLH) protein and a negative transcriptional regulator of p16(INK4a). Expression of Id1 facilitates cellular immortalization and stimulates cell proliferation. With the combination of both specific chemical inhibitors and genetic inhibitors of cell signaling, we showed that induction of Id1 by LMP1 was dependent on its NF-kappaB activation domain at the carboxy-terminal region, CTAR1 and CTAR2. Induction of Id1 by LMP1 may facilitate clonal expansion of premalignant nasopharyngeal epithelial cells infected with EBV and may promote their malignant transformation.