MUTATIONAL ANALYSIS OF TRANSCRIPTIONAL ACTIVATION BY THE BOVINE PAPILLOMAVIRUS TYPE-1 E6

While the bovine papillomavirus type 1 (BPV-1) E6 induces tumorigenic transformation of murine C127 cells, it does not bind or promote the d egradation of p53. We recently showed the cellular protein ERC-55/E6BP binds BPV-1 E6 as well as the cancer-related human papillomavirus (HP V) E6 proteins. BPV-1 E6 also binds E6-AP, a ubiquitin ligase necessar y for HPV E6-induced p53 degradation. We previously reported that the transforming activity of a set of BPV-1 E6 mutants correlated with the ir E6BP-binding ability. Another function of BPV-1 E6 is stimulation o f transcription when targeted to a promoter, although cellular promote rs responsive to BPV-1 E6 have not been identified. To examine whether its transcriptional function is required for oncogenic activity, or i s related to its interactions with E6-AP or E6BP, a series of BPV-1 E6 mutants were analyzed as fusions to a sequence-specific DNA binding d omain for activity in yeast and in mammalian cells. We show that some transformation defective mutants retained substantial levels of transc riptional activation activity, These mutants also distinguish transcri ptional activation from E6-AP and E6BP binding. These results suggest the transcriptional activation function of BPV-1 E6 is not sufficient for cell transformation. (C) 1997 Academic Press.