The Effect And Mechanism Of Papillomavirus E6 Gene On Cellular Apoptosis

Bacground: The bovine papillomavirus type 1 (BPV-1) E6 oncoprotein induces tumorigenic transformation of murinc C127 cells and stimulates transcription when targeted to a promoter. We have previously shown that C127 cells expressing BPV-1 E6 exhibited increased tumor necrosis factor alpha-mediated apoptosis.Aim: To understand the mechanisms by which BPV-1 E6 sensitizes cells to apoptosis and to investigate the relevance of E6-enhanced apoptosis to its other biological activities.Methods: we analyzed a set of BPV-1 E6 mutants for cellular transformation, transcriptional activation, sensitization to apoptosis, and interaction with known cellular binding proteins using a series of assays including MTT, Cell death Elisa, Focus formation, Luciferase and in vitro binding. To this goal, cell lines expressing BPV-1 E6 mutant proteins were established and characterized.Results: Mutants of BPV-1 E6 showed various sensitization ability to TNF induced cell apoptosis. Among them, wild type, R42W and 491 mutants sensitized cells to the apoptosis most dramatically. Wild type and R42W mutant showed strongest cell transformation. K35E and 491 had the most striking transcriptional activation capability, which is similar to wild type. Our data demonstrated that the transcriptional activation function of BPV-1 E6 is necessary but not sufficient for sensitization of cells to apoptosis. Functions required for BPV-1 E6-mediated sensitization of cells to apoptosis are distinct from those required for transformation as well as association with known cellular binding proteins.Conclusion: These results thus indicate that sensitization of cells to TNF-induced apoptosis represents a novel function of BPV-1 E6.