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 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.