The Human Papillomavirus E6 PDZ Binding Motif: From Life Cycle to Malignancy

Viruses

Ketaki Ganti²  Justyna Broniarczyk²  Wiem Manoubi²  Paola Massimi²  Suruchi Mittal²  David Pim²  Anita Szalmas²  Jayashree Thatte²  Miranda Thomas²  Vjekoslav Tomaić²  Lawrence Banks¹ 

[1] International Center for Genetic Engineering and Biotechnology, Area Science Park, Padriciano 99, Trieste 34149, Italy;

关键词: HPV;    E6;    PDZ;    14-3-3;    cell polarity;   

DOI  :  10.3390/v7072785

来源: mdpi

【 摘 要 】

Cancer-causing HPV E6 oncoproteins are characterized by the presence of a PDZ binding motif (PBM) at their extreme carboxy terminus. It was long thought that this region of E6 had a sole function to confer interaction with a defined set of cellular substrates. However, more recent studies have shown that the E6 PBM has a complex pattern of regulation, whereby phosphorylation within the PBM can regulate interaction with two classes of cellular proteins: those containing PDZ domains and the members of the 14-3-3 family of proteins. In this review, we explore the roles that the PBM and its ligands play in the virus life cycle, and subsequently how these can inadvertently contribute towards the development of malignancy. We also explore how subtle alterations in cellular signal transduction pathways might result in aberrant E6 phosphorylation, which in turn might contribute towards disease progression.

【 授权许可】

CC BY   
© 2015 by the authors; licensee MDPI, Basel, Switzerland.