HPV-16 E7 Interacts with the Endocytic Machinery via the AP2 Adaptor μ2 Subunit
Om Basukala, Óscar Trejo-Cerro, Michael P. Myers, David Pim, Paola Massimi, Miranda Thomas, Corrado Guarnaccia, David J. Owen, Lawrence Banks
Abstract
Despite being a very small protein, HPV-E7 has a wide range of functions within the infected cell, many of which can lead to cell transformation. High-risk HPV-E7 deregulates the function of many cellular proteins, perturbing cellular homeostasis. We show that a novel target of HPV-E7 is the clathrin-adaptor protein 2 complex (AP2) μ2 subunit, interacting via residues within E7's pRB-binding region. Mutational studies show that an AP2 recognition motif is present in the CR2 region and is conserved in >50 HPV types, suggesting a common function for this motif in HPV biology. Mutational analysis suggests that this motif is important for cellular transformation, potentially modulating endocytosis of growth factor receptors such as EGFR, and thus being a novel activity of E7 in modulating clathrin-mediated endocytosis and cargo selection. This study has important implications for the molecular basis of E7 function in modulating protein trafficking at the cell surface.