Interactions between E6AP and E6 proteins from alpha and beta HPV types

Abstract

High-risk mucosotropic Human papillomaviruses (HPVs), especially HPV-16, are the aetiological agents of cervical cancer and the cellular targets of their E6 oncoproteins have been much studied. However, much less is known about the cellular targets of the cutaneous HPV E6 proteins. In this study, a proteomic analysis of cells transfected with the E6 proteins from cutaneous HPV types specifically identified E6-interacting proteins involved in the ubiquitination pathways. These include the E3 ubiquitin-protein ligases E6AP and UBR4/p600. We also show that E6AP can contribute towards the steady-state levels of E6 and, conversely, that certain E6 proteins, in addition to those derived from the high-risk mucosal HPV types, can enhance levels of E6AP turnover. These results define important differences and commonalities in how HPV E6 proteins of mucosal and cutaneous origin interact with cellular ubiquitin-protein ligases.