Desaintes C, Demeret C, Goyat S, Yaniv M, Thierry F
Département des Biotechnologies, URA 1644 du CNRS, Institut Pasteur, Paris, France.
EMBO J. 1997 Feb 3;16(3):504-14. doi: 10.1093/emboj/16.3.504.
The papillomavirus E2 protein plays a central role in the viral life cycle as it regulates both transcription and replication of the viral genome. In this study, we showed that transient expression of bovine papillomavirus type 1 or human papillomavirus type 18 (HPV18) E2 proteins in HeLa cells activated the transcriptional activity of p53 through at least two pathways. The first one involved the binding of E2 to its recognition elements located in the integrated viral P105 promoter. E2 binding consequently repressed transcription of the endogenous HPV18 E6 oncogene, whose product has been shown previously to promote p53 degradation. The second pathway did not require specific DNA binding by E2. Expression of E2 induced drastic physiological changes, as evidenced by a high level of cell death by apoptosis and G1 arrest. Overexpression of a p53 trans-dominant-negative mutant abolished both E2-induced p53 transcriptional activation and E2-mediated G1 growth arrest, but showed no effect on E2-triggered apoptosis. These results suggest that the effects of E2 on cell cycle progression and cell death follow distinct pathways involving two different functions of p53.
乳头瘤病毒E2蛋白在病毒生命周期中起着核心作用，因为它调控病毒基因组的转录和复制。在本研究中，我们发现，在HeLa细胞中瞬时表达1型牛乳头瘤病毒或18型人乳头瘤病毒（HPV18）E2蛋白可通过至少两条途径激活p53的转录活性。第一条途径涉及E2与其位于整合病毒P105启动子中的识别元件结合。E2结合因此抑制了内源性HPV18 E6癌基因的转录，其产物先前已被证明可促进p53降解。第二条途径不需要E2进行特异性DNA结合。E2的表达诱导了剧烈的生理变化，这通过高水平的凋亡细胞死亡和G1期阻滞得以证明。p53反式显性负突变体的过表达消除了E2诱导的p53转录激活和E2介导的G1期生长阻滞，但对E2触发的凋亡没有影响。这些结果表明，E2对细胞周期进程和细胞死亡的影响遵循涉及p53两种不同功能的不同途径。
