Thierry F, Yaniv M
UA CNRS 041149, Département de Biologie Moléculaire, Institut Pasteur, Paris, France.
EMBO J. 1987 Nov;6(11):3391-7. doi: 10.1002/j.1460-2075.1987.tb02662.x.
The human papillomavirus 18 (HPV 18) long control region contains promoter and enhancer elements whose activity is restricted to several human cell lines of epithelial origin. This enhancer possesses a considerable constitutive activity which is further stimulated in the presence of the E2 trans-activating protein of bovine papillomavirus 1 (BPV1). Surprisingly the same BPV1 protein strongly repressed transcription from the genuine HPV18 enhancer-promoter DNA sequences. We suggest that binding of several molecules of E2 protein between the viral CAAT and TATA elements sterically hinders transcription initiation from this promoter, while the same DNA--protein assembly stimulates the SV40 promoter when cloned in an enhancer configuration upstream of this heterologous promoter. Unlike BPV1-E2 the homologous E2 gene product does not seem to strongly modulate viral transcription. Finally the BPV1-E2 gene product may repress some essential viral or host genes, since we failed to isolate HeLa cells expressing BPV1-E2.
人乳头瘤病毒18型(HPV 18)的长控制区包含启动子和增强子元件,其活性仅限于几种上皮来源的人类细胞系。该增强子具有相当大的组成型活性,在牛乳头瘤病毒1型(BPV1)的E2反式激活蛋白存在时会进一步增强。令人惊讶的是,相同的BPV1蛋白强烈抑制来自真正的HPV18增强子 - 启动子DNA序列的转录。我们认为,病毒CAAT和TATA元件之间几个E2蛋白分子的结合在空间上阻碍了该启动子的转录起始,而当以增强子构型克隆到该异源启动子上游时,相同的DNA - 蛋白质组装会刺激SV40启动子。与BPV1 - E2不同,同源E2基因产物似乎不会强烈调节病毒转录。最后,BPV1 - E2基因产物可能会抑制一些必需的病毒或宿主基因,因为我们未能分离出表达BPV1 - E2的HeLa细胞。