¹Department of Biochemistry and Microbiology, Center for Molecular Biology and Gene Therapy, Loma Linda University School of Medicine, Loma Linda, CA 92354, USA

Correspondence: PJ Duerksen-Hughes, Department of Biochemistry and Microbiology, Center for Molecular Biology and Gene Therapy, 11085 Campus Street, 121 Mortensen Hall, Loma Linda University School of Medicine, Lorna Linda, CA 92354, USA. Tel: 909/558-4300 ext 81361; Fax: 909/558-0177; E-mail: pdhughes@llu.edu

Received 26 September 2005; Revised 3 January 2006; Accepted 19 January 2006; Published online 10 March 2006.

Abstract

Viruses have developed sophisticated strategies to evade host defenses and facilitate the production and spread of progeny. In this study, we show that transfection of the human papillomavirus (HPV) 16 E6 oncogene into HCT116 cells provides protection from tumor necrosis factor-related apoptosis inducing ligand (TRAIL)-mediated apoptosis. Additionally, we demonstrate that the protection provided by E6 is dose-dependent because higher levels of E6 provide greater protection. The mechanism underlying this protection involves a rapid reduction in the protein levels of both Fas-associated death domain (FADD) and procaspase 8, which results in suppression of the activation of caspases 8, 3 and 2. Interestingly, E6 does not interfere with the mitochondrial apoptotic pathway even though HCT116 cells have been classified as type II cells with regard to TRAIL signaling. These findings demonstrate that E6 has a more generalized effect on signaling by death ligands than was previously thought and support the notion that E6 can utilize p53-independent mechanisms to modulate cell survival.