Desaintes C, Hallez S, Detremmerie O, Burny A
Laboratoire de chimie biologique, Université Libre de Bruxelles, Rhode-St-Genèse, Belgium.
Oncogene. 1995 Jun 1;10(11):2155-61.
High-risk Human Papillomavirus (HPV) E6 and E7 immortalizing oncoproteins are expressed from a promoter tightly regulated by an epithelial specific enhancer. To determine if the p53 tumour suppressor protein can modulate the transcription of these genes, we performed co-transfection experiments with plasmids containing the HPV type 16 or 18 long control regions linked to the chloramphenicol acetyl transferase gene, along with p53 expression vectors. Wild-type, but not mutant, murine or human p53 expression vectors reduced the activity of reporter constructs when co-transfected into HeLa or C33 cell lines. Mutations within the HPV TATA boxes did not significantly alter the levels of p53 repression, suggesting a TATA-independent mechanism. Deletion analyses mapped the p53-responsive domain to the constitutive 230 base pair epithelial specific enhancer. In addition, the enhancer could confer p53-mediated repression when placed upstream of a heterologous promoter.
高危型人乳头瘤病毒（HPV）的E6和E7永生化癌蛋白由一个受上皮特异性增强子严格调控的启动子表达。为了确定p53肿瘤抑制蛋白是否能够调节这些基因的转录，我们将含有与氯霉素乙酰转移酶基因相连的16型或18型HPV长控制区的质粒与p53表达载体进行共转染实验。当野生型而非突变型的鼠类或人类p53表达载体共转染入HeLa或C33细胞系时，报告基因构建体的活性降低。HPV TATA盒内的突变并未显著改变p53的抑制水平，提示存在一种不依赖TATA盒的机制。缺失分析将p53反应域定位到组成型的230碱基对上皮特异性增强子。此外，当该增强子置于异源启动子上游时，可赋予p53介导的抑制作用。
