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Interaction between the HPV E7 oncoprotein and the transcriptional coactivator p300

Abstract

Infection with high-risk human papillomaviruses (HPV) can lead to the development of cervical cancer. This process depends on the interaction of the virus-encoded oncoproteins, E6 and E7, with a variety of host regulatory proteins. As E7 shares both functional and structural similarities with the Adenovirus E1a (Ad E1a) protein, we were interested in investigating the possible interactions between E7 and the transcriptional coactivator p300, since it was originally identified as a target of Ad E1a. Using a variety of assays, we show that E7s from both high- and low-risk HPV types interact with p300. Mutational analysis of E7 maps the site of the interaction to a region spanning the pRb-binding domain and the CKII phosphorylation site. We also map the site of interaction on p300 largely to the CH1 domain. In addition, we demonstrate that the binding between 16E7 and p300 is direct, and can be detected in vivo by coimmunoprecipitation and mammalian two-hybrid assays. Finally, we show that E7 can abolish the p300-mediated E2 transactivation function, suggesting that complex formation between E7 and p300 may contribute to the regulation of E2 transcriptional activity.

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Acknowledgements

We thank Alexandro Marcello and Paola Massimi for their valuable help during experimental work, Tulasiram Prathapam for the His-16E7 construct, Ernesto Guccione for assistance and help in taking confocal images and Miranda Thomas for comments on the manuscript. This work was supported in part by a research grant from the Associazione Italiana per la Ricerca sul Cancro (AIRC) to LB and by a grant to JSM from the Lawson Health Research Institute Internal Research Fund. NA holds a National Science and Engineering Research Council of Canada Studentship. JSM is a Canadian Institutes of Health Research Scholar.

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Correspondence to Lawrence Banks.

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Bernat, A., Avvakumov, N., Mymryk, J. et al. Interaction between the HPV E7 oncoprotein and the transcriptional coactivator p300. Oncogene 22, 7871–7881 (2003). https://doi.org/10.1038/sj.onc.1206896

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Keywords

  • HPV
  • E7
  • p300 transcriptional coactivation

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