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Interaction of the HPV E7 proteins with the pCAF acetyltransferase

Oncogene volume 22, pages 3833–3841 (2003)Cite this article

Abstract

Most cervical carcinomas express the E6 and E7 proteins of a high-risk human papillomavirus (HPV). These proteins affect growth control by interfering with the functions of cell regulatory proteins, promoting oncogenic transformation. A key target of E7 is the tumor suppressor protein pRb, which directly interacts with E7. However, binding to additional cellular regulatory proteins is clearly required for oncogenesis, as mutants of E7 have been identified that bind to pRb, yet fail to transform efficiently. Here we demonstrate the interaction of the HPV 6, 16 and 18 E7 proteins with the pCAF acetyltransferase, which has been reported to function as a coactivator for a variety of transcription factors including p53. Mutation of a highly conserved leucine residue within the zinc finger region of HPV 16 E7 disrupts binding to pCAF and also impairs transformation and transcriptional activation. HPV 16 E7 interacts with the acetyltransferase domain of pCAF, and reduces its acetyltransferase activity in vitro. Our analysis of the interaction between the pCAF acetyltransferase and E7 provides new insight into the mechanisms by which the E7 oncoproteins can alter cellular gene expression and growth.

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Acknowledgements

We thank Mitchell Smith and Mike Christman for encouragement, discussion and reagents. We also thank Greg Wipf, Chris Brandl, Denise Galloway, Yoshihiro Nakatani, Bruce Strober, James Woodgett, Karl Munger and Karen Vousden for their generous gifts of plasmids or strains. This work was supported by grants to JSM from the Cancer Research Society Inc. and the Lawson Health Research Institute Internal Research Fund. NA held a McLaughlin Foundation Studentship, was supported by a Premier's Research Excellence Award, and currently holds a National Science and Engineering Research Council of Canada Studentship. JT is a Fellow of the Pharmaceutical Manufacturers' Association of Canada. JSM is a Canadian Institutes of Health Research Scholar.

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Authors and Affiliations

  1. Department of Microbiology and Immunology, The University of Western Ontario, London Regional Cancer Centre, London, N6A 4L6, Ontario, Canada

    Nikita Avvakumov & Joe S Mymryk

  2. Department of Physiology and Pharmacology, The University of Western Ontario, London Regional Cancer Centre, London, N6A 4L6, Ontario, Canada

    Joe Torchia & Joe S Mymryk

  3. Department of Oncology, The University of Western Ontario, London Regional Cancer Centre, London, N6A 4L6, Ontario, Canada

    Nikita Avvakumov, Joe Torchia & Joe S Mymryk

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  1. Nikita Avvakumov
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Correspondence to Joe S Mymryk.

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Avvakumov, N., Torchia, J. & Mymryk, J. Interaction of the HPV E7 proteins with the pCAF acetyltransferase. Oncogene 22, 3833–3841 (2003). https://doi.org/10.1038/sj.onc.1206562

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