Ubiquitin and ubiquitin-like proteins in HPV-driven carcinogenesis

Abstract Persistent infection with high-risk (HR) human papillomaviruses (HPVs) is responsible for approximately 5% of cancer cases worldwide, including a growing number of oropharyngeal and anogenital cancers. The major HPV oncoproteins, E6 and E7, act together to manipulate cellular pathways involved in the regulation of proliferation, the cell cycle and cell survival, ultimately driving malignant transformation. Protein ubiquitination and the ubiquitin proteasome system (UPS) is often deregulated upon viral infection and in oncogenesis. HPV E6 and E7 interact with and disrupt multiple components of the ubiquitination machinery to promote viral persistence, which can also result in cellular transformation and the formation of tumours. This review highlights the ways in which HPV manipulates protein ubiquitination and the ubiquitin-like protein pathways and how this contributes to tumour development. Furthermore, we discuss how understanding the interactions between HPV and the protein ubiquitination could lead to novel therapeutic targets that are of urgent need in HPV+ carcinomas.