Veterans Affairs Healthcare System, Iowa City, IA 52246, USA.
Virology. 2012 Aug 1;429(2):99-111. doi: 10.1016/j.virol.2012.03.020. Epub 2012 May 1.
The E2 open reading frame of bovine papillomavirus (BPV)-1 encodes a 410 amino acid (aa) transcriptional activator, E2-TA, and collinear polypeptides--E2-TR (243 aa) and E8^E2 (196 aa). E8^E2 and E2-TR share the DNA-binding domain of E2-TA, and both have been defined as transcriptional repressors. Although purified E2-TR and E8^E2 proteins specifically bound E2 sites with similar affinities, only the E2-TR stimulated transcription. Here we show that E2-TR trans-activates E2-dependent promoters 5 to 10-fold in cooperation with cellular factors and in a dose-dependent fashion in epithelial cells and fibroblasts of animal or human origin while E2-TA activated >100-fold and the E8^E2 had no effect. However, in contrast to E2-TA, E2-TR activated transcription from a promoter-proximal position. E2-TR also partially inhibited the BPV-1 P89 or heterologous promoters whereas E8^E2 led to complete repression. Thus, the BPV-1 E2-TR modulates viral gene expression in a manner distinct from other E2 proteins.
牛乳头瘤病毒（BPV）-1 的 E2 开放阅读框编码一个 410 个氨基酸（aa）的转录激活子 E2-TA，以及共线性多肽-E2-TR（243 aa）和 E8^E2（196 aa）。E8^E2 和 E2-TR 共享 E2-TA 的 DNA 结合域，两者都被定义为转录抑制剂。尽管纯化的 E2-TR 和 E8^E2 蛋白特异性地以相似的亲和力结合 E2 位点，但只有 E2-TR 能刺激转录。在这里，我们表明 E2-TR 在与细胞因子协同作用下，在动物或人类来源的上皮细胞和成纤维细胞中以 5 到 10 倍的效率转激活 E2 依赖性启动子，而 E2-TA 则激活 >100 倍，E8^E2 则没有影响。然而，与 E2-TA 不同，E2-TR 从启动子近端位置激活转录。E2-TR 还部分抑制 BPV-1 P89 或异源启动子，而 E8^E2 则导致完全抑制。因此，BPV-1 E2-TR 以不同于其他 E2 蛋白的方式调节病毒基因表达。
