The HPV-16 E7 oncoprotein binds Skip and suppresses its transcriptional activity

E7 is the major transforming protein of human papillomavirus (HPV), which i s implicated in the development of cervical cancer. The transforming activi ty of E7 has been attributed in part to its interaction with the retinoblas toma (Rb) tumour suppressor; however, the Rb interaction alone is not suffi cient for transformation by E7. In a screen for cellular targets of HPV E7, we identified the Ski interacting protein, Skip, as a new interacting part ner of E7. We show that HPV-16 E7 associates with Skip via sequences in its carboxy terminal region, and the evolutionarily conserved proline rich seq uences (PRS) of the SNW domain of Skip. E7 functionally targets Skip in viv o and inhibits its transcriptional activation activity. Two transformation defective mutants of E7 were identified that failed both to bind Skip and t o inhibit its transcriptional activity. These results suggest that inhibiti on of Skip function may contribute to cell transformation by HPV-16 E7.