Induction of the HPV16 enhancer activity by Jun-B and c-Fos through cooperation of the promoter-proximal AP-1 site and the epithelial cell type- specific regulatory element in fibroblasts

The epithelial cell type- specific enhancer of the human papillomavirus (HPV) type 16 termed the long control region (LCR) carries three AP-1 binding sites. We investigated the roles of the AP-1 sites for transactivation of the LCR by Jun-B that may be a cell type specific- transactivator for the HPVs in human fibroblasts in which expression of the endogenous jun-B gene is low. Transient expression of Jun-B alone poorly activated transcriptional activity of the LCR. However, when combined with c-Fos, Jun-B activated the LCR. The promoter-proximal AP-1 site was required for transactivation of the LCR by Jun-B:c-Fos, but the site itself was not sufficient for the maximal response. The proposed cell type specific- regulatory element that harbors binding sites for NF1 as well as TEF-1 and PEA3 motifs, but neither other AP-1 sites nor the proximal enhancer region, could augment the transcriptional response of the promoter-proximal AP-1 site to Jun-B:c-Fos.