title: The bovine papillomavirus E6 protein binds to the LD motif repeats of paxillin and blocks its interaction with vinculin and the focal adhesion kinase.
abstract: The bovine papillomavirus type 1 (BPV-1) E6 oncoprotein can transform fibroblasts and induce anchorage-independent growth and disassembly of the actin stress fibers. We have previously shown that the E6 protein interacts with the focal adhesion protein, paxillin, suggesting a direct role of E6 in the disruption of the actin cytoskeleton. We have now mapped the E6 binding sites on paxillin to the LD motif repeats region, which has been implicated in mediating paxillin binding to two other focal adhesion proteins, vinculin and the focal adhesion kinase. The five LD motif repeats identified in paxillin do not contribute equally to its interaction with E6. The first LD repeat is most critical for paxillin binding to E6 both in vitro and in vivo. Furthermore, the binding of recombinant wild-type E6 protein to paxillin blocked the interaction of several cellular proteins with paxillin, including vinculin and the focal adhesion kinase. A mutant E6 protein (H105) which does not bind to paxillin had no effect on the binding of these cellular proteins to paxillin. These data suggest that E6 disruption of the actin stress fibers occurs through blocking the interaction of paxillin with its cellular effectors such as vinculin and the focal adhesion kinase.
authors.affiliation: Department of Pathology, Harvard Medical School, Boston, Massachusetts 02115, USA.
authors.forename: X
authors.initials: X
authors.lastname: Tong
authors.forename: R
authors.initials: R
authors.lastname: Salgia
authors.forename: J L
authors.initials: JL
authors.lastname: Li
authors.forename: J D
authors.initials: JD
authors.lastname: Griffin
authors.forename: P M
authors.initials: PM
authors.lastname: Howley
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D001665:Binding Sites; D052688:Bovine papillomavirus 1 / Q000378:metabolism*; D002417:Cattle; D015815:Cell Adhesion Molecules / Q000378:metabolism*; D003598:Cytoskeletal Proteins / Q000378:metabolism*; D051416:Focal Adhesion Protein-Tyrosine Kinases; D008969:Molecular Sequence Data; D009856:Oncogene Proteins, Viral / Q000378:metabolism*; D051419:Paxillin; D010750:Phosphoproteins / Q000378:metabolism*; D011505:Protein-Tyrosine Kinases / Q000378:metabolism*; D016596:Vinculin / Q000378:metabolism*
chemical_list: D015815:Cell Adhesion Molecules; D003598:Cytoskeletal Proteins; D009856:Oncogene Proteins, Viral; D051419:Paxillin; D010750:Phosphoproteins; C059269:protein E6, Bovine papillomavirus; D016596:Vinculin; D011505:Protein-Tyrosine Kinases; D051416:Focal Adhesion Protein-Tyrosine Kinases