Papillomavirus E6 and E7 proteins and their cellular targets.
The mucosal human papillomaviruses (HPVs) infect human genital and oral epithelial cells and cause lesions ranging in severity from benign to malignant. HPV associated malignancies include cervical and other anogenital cancers as well as a subpopulation of head and neck cancers. Viral infection of epidermal stem or transit amplifying cells can result in long term viral persistence, and the development of carcinogenesis over a significant amount of time then requires additional cooperating genetic hits. Only the so-called high risk HPV types mediate human carcinogenesis, whereas the low risk HPVs have been linked to benign epithelial lesions that are not generally life threatening, but nonetheless are a major health burden. Expression of the high risk HPV E6 and E7 oncogenes is sufficient for primary human keratinocyte immortalization and is required for initiation and all subsequent stages of carcinogenic progression. Together with the finding that high levels of E6/E7 are a unifying hallmark of HPV positive cancers, these two genes are presumed to be the relevant virus-derived transformation stimuli in humans. E6 and E7 proteins do not possess intrinsic enzymatic activities, but instead function though a number of direct and indirect interactions with cellular proteins, a number of which are well known cellular tumor suppressors. We will summarize here current insights into E6 and E7 interactions with specific cellular targets that stimulate aspects of the viral life cycle, interfere with cell cycle controls and promote carcinogenic processes.
Wise-Draper
Trisha M
TM
Division of Hematology/Oncology, Department of Pediatrics, Cincinnati Children's Hospital Medical Center and The University of Cincinnati College of Medicine, Cincinnati, Ohio 45229, USA.
Wells
Susanne I
SI
D000818:Animals; D045744:Cell Line, Tumor; D002471:Cell Transformation, Neoplastic; D005260:Female; D006801:Humans; D008954:Models, Biological; D009856:Oncogene Proteins, Viral / Q000502:physiology*; D054731:PDZ Domains; D027383:Papillomaviridae / Q000235:genetics / Q000378:metabolism*; D050725:Papillomavirus E7 Proteins / Q000502:physiology*; D030361:Papillomavirus Infections / Q000235:genetics / Q000378:metabolism*; D047428:Protein Kinase Inhibitors / Q000378:metabolism; D016160:Retinoblastoma Protein / Q000378:metabolism; D019098:Telomerase / Q000378:metabolism; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism
C118860:E6 protein, Human papillomavirus type 6; D009856:Oncogene Proteins, Viral; D050725:Papillomavirus E7 Proteins; D047428:Protein Kinase Inhibitors; D016160:Retinoblastoma Protein; D016159:Tumor Suppressor Protein p53; D019098:Telomerase