Wild-type p53 down-regulates transcription from oncogenic human papillomavirus promoters through the epithelial specific enhancer.
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.
Desaintes
C
C
Laboratoire de chimie biologique, Université Libre de Bruxelles, Rhode-St-Genèse, Belgium.
Hallez
S
S
Detremmerie
O
O
Burny
A
A
D002460:Cell Line; D015536:Down-Regulation; D004742:Enhancer Elements, Genetic; D004848:Epithelium / Q000378:metabolism; D006367:HeLa Cells; D006801:Humans; D009154:Mutation; D027383:Papillomaviridae / Q000235:genetics*; D011401:Promoter Regions, Genetic; D014158:Transcription, Genetic; D014162:Transfection; D016159:Tumor Suppressor Protein p53 / Q000235:genetics / Q000502:physiology*
D016159:Tumor Suppressor Protein p53