C-Jun-mediated repression and transactivation of fibronectin

Abstract

Fibronectin (FN) is transactivated by human papillomavirus type 16 (HPV16) E6 via the induction of c-Jun-ATF-2 complexes binding to the cyclic AMP response element (CRE) in the FN promoter. The present study analyzed c-Jun regulation of FN gene expression. Northern and immunoblot analyses showed that c-Jun expression was enhanced in HPV16-E6-expressing cells. However, mouse 10T1/2 cell lines overexpressing c-Jun showed an inverse correlation between the expression levels of c-Jun and those of FN. Luciferase assays indicated that the FN promoter was strongly repressed in c-Jun-overexpressing mouse 10T1/2 cells. Deletion and mutation analyses of the FN promoter revealed that repression of the FN promoter by c-Jun depends on the CRE located at -160 relative to the start site of transcription. Supershift assays of CRE-bound complexes from HPV16-E6-expressing and c-Jun-overexpressing cells suggested that the presence of ATF-2 in the complexes binding to CRE was required for the transactivation of the FN gene. Collectively, our study suggests that the FN gene can be either transactivated or repressed by c-Jun depending on the cell context.