title: 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.
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.
authors.affiliation: Deutsches Krebsforschungszentrum, Heidelberg, Germany.
authors.forename: M I
authors.initials: MI
authors.lastname: Rodríguez
authors.forename: M E
authors.initials: ME
authors.lastname: Finbow
authors.forename: A
authors.initials: A
authors.lastname: Alonso
mesh_terms: D002460:Cell Line; D066246:ErbB Receptors / Q000378:metabolism*; D006801:Humans; D015603:Keratinocytes / Q000166:cytology / Q000378:metabolism; D016296:Mutagenesis; D009856:Oncogene Proteins, Viral / Q000235:genetics / Q000378:metabolism*; D027383:Papillomaviridae / Q000235:genetics / Q000378:metabolism*; D011510:Proteolipids / Q000378:metabolism*; D006180:Proton-Translocating ATPases / Q000378:metabolism*; D025262:Vacuolar Proton-Translocating ATPases; D000086082:Viroporin Proteins
chemical_list: D066246:ErbB Receptors; D009856:Oncogene Proteins, Viral; D011510:Proteolipids; D006180:Proton-Translocating ATPases; D025262:Vacuolar Proton-Translocating ATPases; C054859:oncogene protein E5, Human papillomavirus type 16; D000086082:Viroporin Proteins