title: Viral Interactions with PDZ Domain-Containing Proteins-An Oncogenic Trait?
abstract: Many of the human viruses with oncogenic capabilities, either in their natural host or in experimental systems (hepatitis B and C, human T cell leukaemia virus type 1, Kaposi sarcoma herpesvirus, human immunodeficiency virus, high-risk human papillomaviruses and adenovirus type 9), encode in their limited genome the ability to target cellular proteins containing PSD95/ DLG/ZO-1 (PDZ) interaction modules. In many cases (but not always), the viruses have evolved to bind the PDZ domains using the same short linear peptide motifs found in host protein-PDZ interactions, and in some cases regulate the interactions in a similar fashion by phosphorylation. What is striking is that the diverse viruses target a common subset of PDZ proteins that are intimately involved in controlling cell polarity and the structure and function of intercellular junctions, including tight junctions. Cell polarity is fundamental to the control of cell proliferation and cell survival and disruption of polarity and the signal transduction pathways involved is a key event in tumourigenesis. This review focuses on the oncogenic viruses and the role of targeting PDZ proteins in the virus life cycle and the contribution of virus-PDZ protein interactions to virus-mediated oncogenesis. We highlight how many of the viral associations with PDZ proteins lead to deregulation of PI3K/AKT signalling, benefitting virus replication but as a consequence also contributing to oncogenesis.
authors.affiliation: Institute of Cancer and Genomic Sciences, College of Medical and Dental Sciences, University of Birmingham, Vincent Drive, Birmingham B15 2TT, UK. cdjames@vcu.edu.|Present address; Virginia Commonwealth University, School of Dentistry, W. Baxter Perkinson Jr. Building, 521 North 11th Street, P.O. Box 980566, Richmond, VA 23298-0566, USA. cdjames@vcu.edu.
authors.forename: Claire D
authors.initials: CD
authors.lastname: James
authors.affiliation: Institute of Cancer and Genomic Sciences, College of Medical and Dental Sciences, University of Birmingham, Vincent Drive, Birmingham B15 2TT, UK. s.roberts@bham.ac.uk.
authors.forename: Sally
authors.initials: S
authors.lastname: Roberts
keywords: DLG1; HPV E6; PDZ proteins; PI3K/AKT signalling; SCRIB; adenovirus E4ORF1; cell polarity; oncogenic viruses; tight junctions