Mechanisms of tumor suppressor protein inactivation by the human papillomavirus E6 and E7 oncoproteins

There are now several examples where experimental and epidemiologic data have implied a causative role for viruses in human cancer. Human papillomavirus (HPV) DNA is found in approximately 90% of cervical cancers. Only a subset of the HPV types that infect the anogential tissues, however, are associated with cancer. Interestingly, only the cloned DNA of this subset is capable of immortalizing human primary genital keratinocytes in culture. The oncoproteins of the HPVs are encoded by the E6 and E7 genes. Analogous to the oncoproteins of certain other DNA tumor viruses, the E6 and E7 proteins have been shown to functionally inactivate the tumor suppressor proteins p53 and pRB, respectively. We will review what is known of the mechanisms by which the E6 and E7 proteins inactivate these tumor suppressors and the evidence that these activities are related to the transforming capabilities of the HPVs associated with cancer.