We have generated mutants of bovine papillomavirus type 1 E6 (BE6) that are defective for transcriptional activation and have analyzed these mutants for transformation of contact-inhibited cells and association with the mammalian protein E6-AP. These BE6 mutants demonstrate that transformation by BE6 does not require transcriptional activation and that association of BE6 with E6-AP is a function separable from transcriptional activation by BE6. Association of BE6 with E6-AP appears to be necessary but not sufficient for transformation by BE6. In addition, the mutational analysis of BE6 demonstrates that transactivation, transformation, and association with E6-AP all require sequences throughout the BE6 gene, indicating that the papillomavirus E6 proteins do not have a simple domain structure
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