The HPV-16 E7 oncoprotein binds Skip and suppresses its transcriptional activity.
E7 is the major transforming protein of human papillomavirus (HPV), which is implicated in the development of cervical cancer. The transforming activity of E7 has been attributed in part to its interaction with the retinoblastoma (Rb) tumour suppressor; however, the Rb interaction alone is not sufficient for transformation by E7. In a screen for cellular targets of HPV E7, we identified the Ski interacting protein, Skip, as a new interacting partner of E7. We show that HPV-16 E7 associates with Skip via sequences in its carboxy terminal region, and the evolutionarily conserved proline rich sequences (PRS) of the SNW domain of Skip. E7 functionally targets Skip in vivo and inhibits its transcriptional activation activity. Two transformation defective mutants of E7 were identified that failed both to bind Skip and to inhibit its transcriptional activity. These results suggest that inhibition of Skip function may contribute to cell transformation by HPV-16 E7.
Prathapam
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International Centre for Genetic Engineering and Biotechnology, Padriciano 99, I-34012, Trieste, Italy.
Kühne
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Banks
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D001665:Binding Sites; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism; D006801:Humans; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism*; D056918:Nuclear Receptor Coactivators; D009856:Oncogene Proteins, Viral / Q000235:genetics / Q000378:metabolism*; D027383:Papillomaviridae / Q000378:metabolism*; D050725:Papillomavirus E7 Proteins; D011518:Proto-Oncogene Proteins / Q000235:genetics / Q000378:metabolism; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000378:metabolism; D015534:Trans-Activators / Q000235:genetics / Q000378:metabolism*; D014157:Transcription Factors; D014407:Tumor Cells, Cultured
D004268:DNA-Binding Proteins; D009687:Nuclear Proteins; D056918:Nuclear Receptor Coactivators; D009856:Oncogene Proteins, Viral; D050725:Papillomavirus E7 Proteins; D011518:Proto-Oncogene Proteins; D011993:Recombinant Fusion Proteins; C111791:SNW1 protein, human; D015534:Trans-Activators; D014157:Transcription Factors; C059731:oncogene protein E7, Human papillomavirus type 16; C060614:SKI protein, human