title: Interactions between E6, FAK, and GIT1 at paxillin LD4 are necessary for transformation by bovine papillomavirus 1 E6.
abstract: Bovine papillomavirus 1 E6 interacts with two similar proteins that regulate cell attachment and cell migration called paxillin (PXN) and HIC-5 (also known as HIC5, ARA55, HIC-5, TSC-5, and TGFB1I1). Despite the similarity between HIC-5 and paxillin, paxillin is required for E6 to transform mouse embryo fibroblasts while HIC-5 is not. Using mutants of paxillin, we found that dynamic competitive interactions between E6, focal adhesion kinase, and the GIT1 ARF-GAP protein for binding to paxillin are required but not sufficient for transformation by E6. Using mutants of paxillin and chimeric proteins between HIC-5 and paxillin, we demonstrate that a critical difference between HIC-5 and paxillin is within the LIM domains of paxillin that do not directly interact with E6. Mutational analysis indicates that at least six distinct domains of paxillin are required for E6 transformation.
  
  
  OBJECTIVE
  Papillomaviruses cause epitheliomas in vertebrates through the actions of virus-encoded oncoproteins. Despite the immense diversity of papillomavirus types, our understanding of the mechanisms by which the virus-encoded E6 oncoproteins contribute to cell transformation is restricted to human papillomavirus types that are associated with cancer. Bovine papillomavirus 1 (BPV-1) E6 has served as a model system for studies of E6 structure and function. This study examines the mechanisms by which BPV-1 E6 association with the cellular focal adhesion adapter protein paxillin contributes to cell transformation and extends our knowledge of the diverse mechanisms by which papillomaviruses transform host cells.
authors.affiliation: Department of Pathology, University of Virginia, Charlottesville, Virginia, USA.
authors.forename: Nicole
authors.initials: N
authors.lastname: Brimer
authors.affiliation: Department of Pathology, University of Virginia, Charlottesville, Virginia, USA.
authors.forename: Ramon
authors.initials: R
authors.lastname: Wade
authors.affiliation: Department of Pathology, University of Virginia, Charlottesville, Virginia, USA vandepol@virginia.edu.
authors.forename: Scott
authors.initials: S
authors.lastname: Vande Pol
mesh_terms: D000818:Animals; D052688:Bovine papillomavirus 1 / Q000502:physiology*; D018797:Cell Cycle Proteins / Q000378:metabolism; D002478:Cells, Cultured; D051417:Focal Adhesion Kinase 1 / Q000378:metabolism; D020690:GTPase-Activating Proteins / Q000378:metabolism; D051379:Mice; D009856:Oncogene Proteins, Viral / Q000378:metabolism*; D051419:Paxillin / Q000378:metabolism*; D025941:Protein Interaction Mapping
chemical_list: D018797:Cell Cycle Proteins; D020690:GTPase-Activating Proteins; C120766:Git1 protein, mouse; D009856:Oncogene Proteins, Viral; D051419:Paxillin; C059269:protein E6, Bovine papillomavirus; D051417:Focal Adhesion Kinase 1; C496051:Ptk2 protein, mouse