Wood V H J, O'Neil J D, Wei W, Stewart S E, Dawson C W, Young L S
Cancer Research UK Institute for Cancer Studies, University of Birmingham, Edgbaston, Birmingham, UK.
Oncogene. 2007 Jun 14;26(28):4135-47. doi: 10.1038/sj.onc.1210496. Epub 2007 May 7.
The Epstein-Barr virus (EBV)-encoded EBNA1 protein is expressed in all virus-associated tumors where it plays an essential role in the maintenance, replication and transcription of the EBV genome. Transcriptional profiling of EBNA1-expressing carcinoma cells demonstrated that EBNA1 also influences the expression of a range of cellular genes including those involved in translation, transcription and cell signaling. Of particular interest was the ability of EBNA1 to enhance expression of STAT1 and sensitize cells to interferon-induced STAT1 activation with resultant enhancement of major histocompatibility complex expression. A negative effect of EBNA1 on the expression of TGFbeta1-responsive betaig-h3 and PAI-1 genes was confirmed at the protein level in EBV-infected carcinoma cells. This effect resulted from the ability of EBNA1 to repress TGFbeta1-induced transcription via a reduction in the interaction of SMAD2 with SMAD4. More detailed analysis revealed that EBNA1 induces a lower steady-state level of SMAD2 protein as a consequence of increased protein turnover. These data show that EBNA1 can influence cellular gene transcription resulting in effects that may contribute to the development of EBV-associated tumors.
爱泼斯坦-巴尔病毒（EBV）编码的EBNA1蛋白在所有与病毒相关的肿瘤中均有表达，它在EBV基因组的维持、复制和转录过程中发挥着至关重要的作用。对表达EBNA1的癌细胞进行转录谱分析表明，EBNA1还会影响一系列细胞基因的表达，包括那些参与翻译、转录和细胞信号传导的基因。特别值得关注的是，EBNA1能够增强STAT1的表达，并使细胞对干扰素诱导的STAT1激活敏感，从而导致主要组织相容性复合体表达增强。在EBV感染的癌细胞中，从蛋白质水平证实了EBNA1对TGFβ1反应性βig-h3和PAI-1基因表达具有负面影响。这种效应是由于EBNA1通过减少SMAD2与SMAD4的相互作用来抑制TGFβ1诱导的转录所致。更详细的分析表明，由于蛋白质周转增加，EBNA1会诱导SMAD2蛋白的稳态水平降低。这些数据表明，EBNA1可影响细胞基因转录，其产生的效应可能有助于EBV相关肿瘤的发展。
