Li H M, Zhuang Z H, Wang Q, Pang J C S, Wang X H, Wong H L, Feng H C, Jin D Y, Ling M T, Wong Y C, Eliopoulos A G, Young L S, Huang D P, Tsao S W
Department of Anatomy, The University of Hong Kong, 21 Sassoon Road, Hong Kong SAR, China.
Oncogene. 2004 May 27;23(25):4488-94. doi: 10.1038/sj.onc.1207580.
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.
鼻咽癌与爱泼斯坦-巴尔病毒（EBV）感染密切相关。EBV编码的LMP1具有细胞转化特性。它可抑制细胞衰老并提高多种细胞类型的细胞存活率。LMP1表达的许多下游事件是通过其激活核因子κB的能力介导的。在本研究中，我们报道了LMP1在鼻咽上皮细胞（NP69）和人胚肾细胞（HEK293）中诱导Id1表达的新功能。Id1是一种碱性螺旋-环-螺旋（bHLH）蛋白，是p16（INK4a）的负性转录调节因子。Id1的表达促进细胞永生化并刺激细胞增殖。通过细胞信号传导的特异性化学抑制剂和基因抑制剂相结合，我们发现LMP1对Id1的诱导依赖于其羧基末端区域的核因子κB激活结构域CTAR1和CTAR2。LMP1对Id1的诱导可能促进感染EBV的癌前鼻咽上皮细胞的克隆扩增，并可能促进其恶性转化。
