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Human papillomavirus E7 proteins stimulate proliferation independently of their ability to associate with retinoblastoma protein

Oncogene volume 19, pages 821–826 (2000)Cite this article

Abstract

Studies on human papillomavirus type 16 have demonstrated that the product of the early gene, E7, plays a key role in the immortalization and malignant transformation of the host cell. Several of the biological activities of HPV16 E7 are mediated by inactivation of the members of the pocket protein family, pRb, p107 and p130. In this study, we have characterized the in vitro properties of five E7 proteins from benign and malignant HPV types (10, 32, 48, 54, 77). We show that these E7 proteins associate with pRb and p107 with different efficiencies. All E7s increased the proliferative rate of immortalized rodent fibroblasts cultured in 10% calf serum containing medium. This property is completely independent of their ability to associate with the pocket proteins. Furthermore, all E7s, except HPV10 E7, stimulate G1/S progression and activated the cyclin E and cyclin A promoter in the absence of growth factors. This activity also does not correlate with the E7-efficiency of binding the pocket proteins. Together these data provide evidence that different E7s alter the regulation of the cell cycle by diverse mechanism(s). Finally, this comparative analysis of the different E7 proteins demonstrates that the oncogenicity of a HPV type is not determined by the ability of E7 to associate with the pocket proteins.

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Acknowledgements

We express our gratitude to Professor Harald zur Hausen for his constant support during the course of this work. We would like to thank all the members of our laboratory for their co-operation, Dr Pidder Jansen-Dürr for the plasmids containing cyclin E and A promoters and Dr Leonie Ringrose for her constructive comments on the manuscript. SC was supported by a PRAXIS XXI doctoral fellowship (Sub Programa Ciencia e Tecnologia do 2° Quadro Comunitario de Apoio).

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  1. Angewandte Tumorvirologie, Deutsches Krebsforschungszentrum, INF 242, Heidelberg, D-69120, Germany

    Sandra Caldeira, Ethel-Michele de Villiers & Massimo Tommasino

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  1. Sandra Caldeira
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Caldeira, S., de Villiers, EM. & Tommasino, M. Human papillomavirus E7 proteins stimulate proliferation independently of their ability to associate with retinoblastoma protein. Oncogene 19, 821–826 (2000). https://doi.org/10.1038/sj.onc.1203375

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