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

Oncogene volume 20, pages 7677–7685 (2001)Cite this article

Abstract

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.

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Acknowledgements

We are very grateful to Paola Massimi and David Pim for the Δ52–56 E7 mutant and their help and advice. We are also very grateful to Mike Hayman for his gift of pCGSP-Skip and pMT2-Ski expression plasmids. We would like to thank Gianni del Sal for the pRb expression construct and Mauro Sturnega for the help in the production of antibodies. We would also like to thank Miranda Thomas for her comments on the manuscript. This work was supported in part by research grants from the Associazione Italiana per la Ricerca Sul Cancro and the EU Biomed 2 program.

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  1. International Centre for Genetic Engineering and Biotechnology, Padriciano 99, Trieste, I-34012, Italy

    Tulasiram Prathapam, Christian Kühne & Lawrence Banks

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  1. Tulasiram Prathapam
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Prathapam, T., Kühne, C. & Banks, L. The HPV-16 E7 oncoprotein binds Skip and suppresses its transcriptional activity. Oncogene 20, 7677–7685 (2001). https://doi.org/10.1038/sj.onc.1204960

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