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UVB irradiation reduces the half-life and transactivation potential of the human papillomavirus 16 E2 protein

Oncogene volume 22, pages 4469–4477 (2003)Cite this article

Abstract

Human papillomaviruses (HPV) are causative agents of human cancers including those of the cervix and also of the head and neck; HPV16 is the most commonly found type in these diseases. The viral E2 protein regulates transcription from the viral genome by interacting with DNA-binding sequences in the HPV transcriptional control region; it also regulates replication by interacting with and recruiting the HPV replication factor E1 to the viral origin. Therefore, E2 is essential for the viral life cycle. The E2 protein interacts with several proteins involved in the cellular response to DNA damage including p53, TopBP1, and PARP. We therefore set out to establish whether DNA-damaging agents can regulate E2 activity. Here we show that UVB irradiation downregulates transcriptional activity of both HPV16 and HPV8 E2, while hydroxyurea and etoposide do not. This downregulation of E2 activity is independent of p53 function as it occurs in p53 wild type and null cell types as well as in the presence of functional HPV16 E6 that degrades p53. Using stable cell lines expressing E2 we show that this downregulation of E2 function by UVB is due to a reduction of the E2 protein half-life. The identification of the pathway(s) through which UVB downregulates E2 transcriptional activity and protein levels will present a novel target for the treatment of HPV-related diseases.

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Acknowledgements

We would like to thank Professors Saveria Campo and John Wyke for a critical reading of the manuscript, and Dr Merlyn Hibma for the TVG 261 antibody. We also thank the late Professor Pawel Fuchs who kindly provided us with the HPV8 E2 expression vectors. This work was supported by the Scottish Hospitals Endowment Research Trust, the Royal Society, and the Biotechnology and Biological Sciences Research Council.

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  1. Department of Veterinary Pathology, Institute of Comparative Medicine, University of Glasgow, Garscube Estate, Bearsden Road, Glasgow, G61 1QH, Scotland, UK

    Ewan R Taylor, Winifred Boner, Edward S Dornan, Eilidh M Corr & Iain M Morgan

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  1. Ewan R Taylor
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  2. Winifred Boner
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Correspondence to Iain M Morgan.

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Taylor, E., Boner, W., Dornan, E. et al. UVB irradiation reduces the half-life and transactivation potential of the human papillomavirus 16 E2 protein. Oncogene 22, 4469–4477 (2003). https://doi.org/10.1038/sj.onc.1206746

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