title: The Human Papillomavirus E6 PDZ Binding Motif: From Life Cycle to Malignancy.
abstract: 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.
authors.affiliation: International Center for Genetic Engineering and Biotechnology, Area Science Park, Padriciano 99, Trieste 34149, Italy. ganti@icgeb.org.
authors.forename: Ketaki
authors.initials: K
authors.lastname: Ganti
authors.affiliation: International Center for Genetic Engineering and Biotechnology, Area Science Park, Padriciano 99, Trieste 34149, Italy. justekbr@amu.edu.pl.
authors.forename: Justyna
authors.initials: J
authors.lastname: Broniarczyk
authors.affiliation: International Center for Genetic Engineering and Biotechnology, Area Science Park, Padriciano 99, Trieste 34149, Italy. wiem.manoubi@yahoo.fr.
authors.forename: Wiem
authors.initials: W
authors.lastname: Manoubi
authors.affiliation: International Center for Genetic Engineering and Biotechnology, Area Science Park, Padriciano 99, Trieste 34149, Italy. paola@icgeb.org.
authors.forename: Paola
authors.initials: P
authors.lastname: Massimi
authors.affiliation: International Center for Genetic Engineering and Biotechnology, Area Science Park, Padriciano 99, Trieste 34149, Italy. mittal@icgeb.org.
authors.forename: Suruchi
authors.initials: S
authors.lastname: Mittal
authors.affiliation: International Center for Genetic Engineering and Biotechnology, Area Science Park, Padriciano 99, Trieste 34149, Italy. pim@icgeb.org.
authors.forename: David
authors.initials: D
authors.lastname: Pim
authors.affiliation: International Center for Genetic Engineering and Biotechnology, Area Science Park, Padriciano 99, Trieste 34149, Italy. aszalmas@med.unideb.hu.
authors.forename: Anita
authors.initials: A
authors.lastname: Szalmas
authors.affiliation: International Center for Genetic Engineering and Biotechnology, Area Science Park, Padriciano 99, Trieste 34149, Italy. thatte@icgeb.org.
authors.forename: Jayashree
authors.initials: J
authors.lastname: Thatte
authors.affiliation: International Center for Genetic Engineering and Biotechnology, Area Science Park, Padriciano 99, Trieste 34149, Italy. miranda@icgeb.org.
authors.forename: Miranda
authors.initials: M
authors.lastname: Thomas
authors.affiliation: International Center for Genetic Engineering and Biotechnology, Area Science Park, Padriciano 99, Trieste 34149, Italy. tomaic@icgeb.org.
authors.forename: Vjekoslav
authors.initials: V
authors.lastname: Tomaić
authors.affiliation: International Center for Genetic Engineering and Biotechnology, Area Science Park, Padriciano 99, Trieste 34149, Italy. banks@icgeb.org.
authors.forename: Lawrence
authors.initials: L
authors.lastname: Banks
mesh_terms: D052685:Alphapapillomavirus / Q000737:chemistry / Q000235:genetics / Q000254:growth & development / Q000378:metabolism*; D000818:Animals; D006801:Humans; D009369:Neoplasms / Q000821:virology; D009856:Oncogene Proteins, Viral / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D054731:PDZ Domains; D030361:Papillomavirus Infections / Q000821:virology*; D010766:Phosphorylation
chemical_list: D009856:Oncogene Proteins, Viral
keywords: 14-3-3; E6; HPV; PDZ; cell polarity