title: Bovine papillomavirus E7 transformation function correlates with cellular p600 protein binding.
abstract: The E7 oncoprotein of bovine papillomavirus type 1 (BPV-1) is required for the full transformation activity of the virus. However, the mechanism by which E7 contributes to cellular transformation is unknown. To address this question, we used the proteomic approach of tandem affinity purification to identify cellular proteins that are in complex with E7, and identified the 600-kDa protein, p600, as a binding partner of E7. The ability of E7 to complex with p600 correlated with its ability to enhance anchorage independence of BPV-1 E6-expressing cells. Furthermore, E7 mutant proteins impaired in their ability to bind p600 were transformation defective. Additionally, knockdown of p600 reduced transformation of cells expressing both BPV-1 E6 and E7, as well as E6 alone, suggesting that the ability of E7 to transformed cells is mediated, at least in part, through its ability to bind p600. These data complement work that shows that HPV16 E7 also interacts with p600, and that this interaction correlates with the ability of HPV16 E7 to transform cells. These studies thus identify p600 as a shared target of the E7 proteins of multiple papillomaviruses.
authors.affiliation: Department of Pathology, Brigham and Women's Hospital and Department of Medicine, Harvard Medical School, Boston, MA 02115, USA.
authors.forename: Joseph
authors.initials: J
authors.lastname: DeMasi
authors.forename: Kyung-Won
authors.initials: KW
authors.lastname: Huh
authors.forename: Yoshihiro
authors.initials: Y
authors.lastname: Nakatani
authors.forename: Karl
authors.initials: K
authors.lastname: Münger
authors.forename: Peter M
authors.initials: PM
authors.lastname: Howley
mesh_terms: D000595:Amino Acid Sequence; D052688:Bovine papillomavirus 1 / Q000378:metabolism*; D002148:Calmodulin-Binding Proteins / Q000378:metabolism*; D002472:Cell Transformation, Viral / Q000502:physiology*; D015151:Immunoblotting; D047468:Immunoprecipitation; D008969:Molecular Sequence Data; D046912:Multiprotein Complexes / Q000302:isolation & purification / Q000378:metabolism*; D009856:Oncogene Proteins, Viral / Q000235:genetics / Q000378:metabolism*; D034622:RNA Interference; D016415:Sequence Alignment
chemical_list: D002148:Calmodulin-Binding Proteins; D046912:Multiprotein Complexes; D009856:Oncogene Proteins, Viral; C075621:oncogene protein E7, Bovine papillomavirus type 1