Mechanism of HPV E6 proteins in cellular transformation

The E6 protein is a major transforming protein of many types of papillomaviruses. Mechanistically, the best characterized Eb proteins are those of the high-risk genital HPVs (e.g. HPV-16 and 18 E6), which function, at least in part, by inactivating the p53 tumor suppressor protein. Biochemical studies have shown that this occurs by targeted degradation of p53, dependent on the EG-A6 ubiquitin-protein ligase. The model that has emerged from E6/E6-AP-dependent p53 degradation has provided insight into both HPV-associated carcinogenesis and the problem of substrate specificity of the ubiquitin system. Several observations suggest that the high-risk HPV E6 proteins may also have activities in addition to inactivation of p53. (C) 1997 Academic Press Ltd.