title: Papillomavirus E7 oncoproteins share functions with polyomavirus small T antigens.
abstract: Many of the small DNA tumor viruses encode transforming proteins that function by targeting critical cellular pathways involved in cell proliferation and survival. In this study, we have examined whether some of the functions of the polyomavirus small T antigens (ST) are shared by the E6 and E7 oncoproteins of two oncogenic papillomaviruses. Using three different assays, we have found that E7 can provide some simian virus 40 (SV40) or murine polyomavirus (PyV) ST functions. Both human papillomavirus 16 (HPV16) and bovine papillomavirus (BPV1) E7 proteins are capable of partially substituting for SV40 ST in a transformation assay that also includes SV40 large T antigen, the catalytic subunit of cellular telomerase, and oncogenic Ras. Like SV40 ST, HPV16 E7 has the ability to override a quiescence block induced by mitogen deprivation. Like PyV ST, it also has the ability to inhibit myoblast differentiation. At least two of these activities are dependent upon the interaction of HPV16 E7 with retinoblastoma protein family members. For small T antigens, interaction with PP2A is needed for each of these functions. Even though there is no strong evidence that E6 or E7 share the ability of small T to interact with PP2A, E7 provides these functions related to cellular transformation.
  
  
  OBJECTIVE
  DNA tumor viruses have provided major insights into how cancers develop. Some viruses, like the human papillomaviruses, can cause cancer directly. Both the papillomaviruses and the polyomaviruses have served as tools for understanding pathways that are often perturbed in cancer. Here, we have compared the functions of transforming proteins from several DNA tumor viruses, including two papillomaviruses and two polyomaviruses. We tested the papillomavirus E6 and E7 oncoproteins in three functional assays and found that E7 can provide some or all of the functions of the SV40 small T antigen, another well-characterized oncoprotein, in two of these assays. In a third assay, papillomavirus E7 has the same effect as the murine polyomavirus small T protein. In summary, we report several new functions for the papillomavirus E7 proteins, which will contribute new insights into the roles of viruses in cancer and the cellular pathways they perturb in carcinogenesis.
authors.affiliation: Department of Microbiology and Immunobiology, Harvard Medical School, Boston, Massachusetts, USA.
authors.forename: Elizabeth A
authors.initials: EA
authors.lastname: White
authors.affiliation: Department of Microbiology and Immunobiology, Harvard Medical School, Boston, Massachusetts, USA.
authors.forename: Rebecca E
authors.initials: RE
authors.lastname: Kramer
authors.affiliation: Department of Developmental, Molecular & Chemical Biology, Tufts University School of Medicine, Boston, Massachusetts, USA.
authors.forename: Justin H
authors.initials: JH
authors.lastname: Hwang
authors.affiliation: Departments of Cancer Biology and Medical Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, Massachusetts, USA.
authors.forename: Arun T
authors.initials: AT
authors.lastname: Pores Fernando
authors.affiliation: Departments of Cancer Biology and Medical Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, Massachusetts, USA.
authors.forename: Nana
authors.initials: N
authors.lastname: Naetar
authors.affiliation: Departments of Cancer Biology and Medical Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, Massachusetts, USA.
authors.forename: William C
authors.initials: WC
authors.lastname: Hahn
authors.affiliation: Departments of Cancer Biology and Medical Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, Massachusetts, USA.
authors.forename: Thomas M
authors.initials: TM
authors.lastname: Roberts
authors.affiliation: Department of Developmental, Molecular & Chemical Biology, Tufts University School of Medicine, Boston, Massachusetts, USA.
authors.forename: Brian S
authors.initials: BS
authors.lastname: Schaffhausen
authors.affiliation: Departments of Cancer Biology and Medical Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, Massachusetts, USA.
authors.forename: David M
authors.initials: DM
authors.lastname: Livingston
authors.affiliation: Department of Microbiology and Immunobiology, Harvard Medical School, Boston, Massachusetts, USA peter_howley@hms.harvard.edu.
authors.forename: Peter M
authors.initials: PM
authors.lastname: Howley
mesh_terms: D000952:Antigens, Polyomavirus Transforming / Q000378:metabolism*; D002472:Cell Transformation, Viral; D005816:Genetic Complementation Test; D052162:Human papillomavirus 16 / Q000235:genetics / Q000502:physiology; D006801:Humans; D009856:Oncogene Proteins, Viral / Q000235:genetics / Q000378:metabolism* / Q000502:physiology; D050725:Papillomavirus E7 Proteins / Q000378:metabolism*; D012097:Repressor Proteins / Q000378:metabolism*; D013539:Simian virus 40 / Q000235:genetics / Q000502:physiology
chemical_list: D000952:Antigens, Polyomavirus Transforming; C068651:E6 protein, Human papillomavirus type 16; D009856:Oncogene Proteins, Viral; D050725:Papillomavirus E7 Proteins; D012097:Repressor Proteins; C075621:oncogene protein E7, Bovine papillomavirus type 1; C059731:oncogene protein E7, Human papillomavirus type 16