Abstract
Human papillomavirus type 16 E5 protein (HPV16 E5) upregulates ligand-mediated activation of the epidermal growth factor receptor (EGFR) in transfected human keratinocytes. HPV16 E5 binds to the 16 kDa proteolipid (subunit c) of the vacuolar H+-ATPase (16K), responsible for endosomal acidification, and this binding has been suggested to be responsible for increased recycling of the EGFRs. Using mutant deletions we show here that amino acids 54–78, but not 79–83 are necessary for binding to the 16K proteolipid. EGF treatment of cells expressing wild type or mutants of the E5 protein show that deletion of the last carboxy terminal 5 amino acids results in loss of E5-mediated EGFR overactivation. Thus, our results show that the binding capacity of HPV16 E5 to 16K can be dissociated from the effect of the viral protein on EGFR activation.
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Acknowledgements
We would like to thank Pauline McLean and Jürgen Fisher for technical assistance and Dr Chris Bartholomew for reading the manuscript. This work was supported in part by the Cancer Research Campaign.
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Rodríguez, M., Finbow, M. & Alonso, A. Binding of human papillomavirus 16 E5 to the 16 kDa subunit c (proteolipid) of the vacuolar H+-ATPase can be dissociated from the E5-mediated epidermal growth factor receptor overactivation. Oncogene 19, 3727–3732 (2000). https://doi.org/10.1038/sj.onc.1203718
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DOI: https://doi.org/10.1038/sj.onc.1203718
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