Department of Microbiology and Tumor Virology Program, Abramson Comprehensive Cancer Center, School of Medicine, University of Pennsylvania, 202E Johnson Pavilion, 3610 Hamilton Walk, Philadelphia, PA 19104, USA.
Virology. 2011 Feb 5;410(1):64-75. doi: 10.1016/j.virol.2010.10.029. Epub 2010 Nov 19.
Resistance to apoptosis is an important component of the overall mechanism which drives the tumorigenic process. EBV is a ubiquitous human gamma-herpesvirus which preferentially establishes latent infection in viral infected B-lymphocytes. EBNA1 is typically expressed in most forms of EBV-positive malignancies and is important for replication of the latent episome in concert with replication of the host cells. Here, we investigate the effects of EBNA1 on survivin up-regulation in EBV-infected human B-lymphoma cells. We present evidence which demonstrates that EBNA1 forms a complex with Sp1 or Sp1-like proteins bound to their cis-element at the survivin promoter. This enhances the activity of the complex and up-regulates survivin. Knockdown of survivin and EBNA1 showed enhanced apoptosis in infected cells and thus supports a role for EBNA1 in suppressing apoptosis in EBV-infected cells. Here, we suggest that EBV encoded EBNA1 can contribute to the oncogenic process by up-regulating the apoptosis suppressor protein, survivin in EBV-associated B-lymphoma cells.
抵抗细胞凋亡是驱动肿瘤发生过程的整体机制的重要组成部分。EBV 是一种普遍存在的人类γ疱疹病毒，它优先在病毒感染的 B 淋巴细胞中建立潜伏感染。EBNA1 通常在大多数形式的 EBV 阳性恶性肿瘤中表达，对于与宿主细胞复制一致的潜伏外显子的复制是重要的。在这里，我们研究了 EBNA1 对 EBV 感染的人类 B 淋巴瘤细胞中 survivin 上调的影响。我们提供的证据表明，EBNA1 与结合到 survivin 启动子上的顺式元件的 Sp1 或 Sp1 样蛋白形成复合物。这增强了复合物的活性并上调了 survivin。 survivin 和 EBNA1 的敲低显示感染细胞中的细胞凋亡增加，因此支持 EBNA1 在抑制 EBV 感染细胞中的细胞凋亡中的作用。在这里，我们提出 EBV 编码的 EBNA1 可以通过上调凋亡抑制蛋白 survivin 在 EBV 相关 B 淋巴瘤细胞中促进致癌过程。
