E6-AP Directs the HPV E6-dependent Inactivation of p53 and Is Representative of a Family of Structurally and Functionally Related Proteins

There are now several examples where experimental and/or epidemiologic data have implied a causative role for viruses in human cancer. Human papillomavirus (HPV) DNA has been found in approximately 90% of cervical cancers. Only a subset of the approximately 20 distinct HPV types that infect the anogenital tissues, however, are generally found in cervical cancers. This has led to the classification of anogenital-specific HPV types into "high risk" and "low risk" groups (DeVilliers 1989; zur Hausen 1991). This classification is reflected in cell culture in that only the cloned DNA of the high-risk HPVs (HPV-16 and -18, for example) is capable of immortalizing human primary genital keratinocytes, the normal host cell (Dürst et al. 1987; Münger et al. 1989). The E6 and E7 genes are the viral genes that are generally expressed in HPV-containing cancers and are together necessary and sufficient for immortalization of primary keratinocytes (Hawley-Nelson et al. 1989;...