Bovine papillomavirus E5 oncoprotein binds to the 16K component of vacuolar H+-ATPases

Abstract

THE major transforming protein of bovine papillomavirus type 1, á£5 (refs 1–4), is mainly associated with endomembranes^{5, 6}, specifically binding to a cellular protein of relative molecular mass 16,000 (16K) (ref. 7). At the same time as transformation, E5 causes the phosphorylation of tyrosine residues in epidermal and platelet-derived growth factor receptors^{8, 9}. We show here that the 16K protein associated with E5 is the 16K component of vacuolar ATPases. This protein is known to be an integral membrane protein in endosomes, bovine chromaffin granules, synaptic vesicles, fungal and plant vacuoles and clathrin-coated vesicles^10–16, as well as a component of gap-junction-like membrane complexes¹⁷. Because proton pumps are critical for the function of cellular compartments that process growth-factor receptors, the interaction of E5 with the 16K protein could explain the pleiomorphic features of cells transformed by E5.