Structure, Activity, and Regulation of the Bovine Papillomavirus E5 Gene and Its Transforming Protein Product

  • B. H. Horwitz
  • J. Settleman
  • S. S. Prakash
  • D. DiMaio
Part of the Current Topics in Microbiology and Immunology book series (CT MICROBIOLOGY, volume 144)


Transfected bovine papillomavirus type 1 (BPV) DNA can induce tumorigenic transformation of C127 cells, an established line of mouse cells (Dvoretsky et al. 1980; Lowy et al. 1980). By assaying the activity of constructed viral mutants, we and others have shown that an intact E5 gene is required for efficient C127 cell focus formation (DiMaio et al. 1986; Groff and Lancaster 1986; Rabson et al. 1986). Moreover, expression of the E5 gene in the absence of all other BPV genes is sufficient to induce focus formation (Schiller et al. 1986; Yang et al. 1985; Horwitz et al. 1988). Detailed mutational and biochemical analysis of this gene indicates that translation of the portion of open reading frame (ORF) E5 downstream of the first methionine codon results in the synthesis of a 7K polypeptide required for efficient transformation (DiMaio et al. 1986; Schlegel et al. 1986; Burkhardt et al. 1987).


Cl27 Cell Transformation Defect Long Control Region Tumorigenic Transformation CMT4 Cell 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. Androphy EJ, Lowy DR, Schiller JS (1987) Bovine papillomavirus E2 trans-activating gene product binds to specific site in papillomavirus DNA. Nature 325: 70–73PubMedCrossRefGoogle Scholar
  2. Burkhardt A, DiMaio D, Schlegel R (1987) Genetic and biochemical definition of the bovine papillomavirus E5 transforming protein. EMBO J 8: 2381–2385Google Scholar
  3. DiMaio D (1986) Nonsense mutation in open reading frame E2 of bovine papillomavirus DNA. J Virol 57: 475–480PubMedGoogle Scholar
  4. DiMaio D, Guralski D, Schiller JT (1986) Translation of open reading frame E5 of bovine papillomavirus is required for its transforming activity. Proc Natl Acad Sci USA 83: 1797–1801PubMedCrossRefGoogle Scholar
  5. Dvoretzky I, Shoher R, Chattopadhyay SK, Lowy DH (1980) A quantitative focus forming assay for bovine papilloma virus Virology 103: 369–375PubMedCrossRefGoogle Scholar
  6. Green M, Lowenstein PM (1987) Demonstration that a chemically synthesized BPV1 oncoprotein and its C-terminal domain function to induce cellular DNA synthesis. Cell 51: 795–802PubMedCrossRefGoogle Scholar
  7. Groff DE, Lancaster WD (1986) Genetic analysis of the 3’ early region transformation and replication functions of bovine papillomavirus type 1. Virology 150: 221–230PubMedCrossRefGoogle Scholar
  8. Haugen TH, Cripe TP, Ginder GD, Karin M, Turek LP (1987) Trans-activation of an upstream early gene promoter by bovine papillomavirus 1 by a product of the viral E2 gene. EMBO J 6: 145–152PubMedGoogle Scholar
  9. Horwitz BH, Burkhardt AL, Schlegel R, DiMaio D (1988) 44-Amino acid E5 transforming protein of bovine papillomavirus requires a hydrophobic core and specific carboxyl-terminal amino acids. Mol Cell Biol 8: 4071–4078PubMedGoogle Scholar
  10. Kleiner E, Dietrich W, Pfister H (1986) Differential regulation of papillomavirus early gene products in transformed fibroblasts and carcinoma cell lines. EMBO J 5: 1945–1950PubMedGoogle Scholar
  11. Lambert PF, Spalholz BA, Howley PM (1987) A transcriptional repressor encoded by BPV-1 shares a common carboxy terminal domain with the E2 transactivation Cell 50: 69–78PubMedCrossRefGoogle Scholar
  12. Lowy DR, Dvoretzky I, Shober R, Law MF, Engel L, Howley PM (1980) In vitro tumorigenic transformation by a defined subgenomic fragment of bovine papilloma virus DNA. Nature 287: 72–74PubMedCrossRefGoogle Scholar
  13. Lusky M, Botchan MR (1985) Genetic analysis of bovine papillomavirus type 1 trans-acting replication factors. J Virol 53: 955–965PubMedGoogle Scholar
  14. Moskaluk C, Bastia D (1987) The E2 “gene” of bovine papillomavirus encodes an enhancer binding protein. Proc Natl Acad Sci USA 84: 1215–1218PubMedCrossRefGoogle Scholar
  15. Prakash SS, Horwitz BH, Zibello T, Settleman J, DiMaio D (1988) Bovine papillomavirus E2 gene regulates the expression of the viral E5 transforming gene. J. Virology 62: 3608–3613PubMedGoogle Scholar
  16. Rabson MS, Yee C, Yang Y-C, Howley PM (1986) Bovine papillomavirus type 1 3’ early region transformation and plasmid maintenance functions. J Virol 60: 626–634PubMedGoogle Scholar
  17. Schiller JT, Vass WC, Vousdan KH, Lowy DR (1986) The E5 open reading frame of bovine papillomavirus type 1 encodes a transforming gene. J Virol 57: 1–6PubMedGoogle Scholar
  18. Schlegel R, Wade-Glass M, Rabson MS, Yang Y-C (1986) The E5 transforming gene of bovine papillomavirus encodes a small hydrophobic polypeptide. Science 233: 464–467PubMedCrossRefGoogle Scholar
  19. Settleman J, DiMaio D (1988) Efficient transactivation and morphologic transformation by bovine papillomavirus genes expressed from a BPV/SV40 recombinant virus. Proc Natl Acad Sci USA 85: 9007–9011PubMedCrossRefGoogle Scholar
  20. Spalholz BA, Yang YC, Howley PM (1985) transactivation of a bovine papillomavirus transcriptional regulatory element by the E2 gene product. Cell 42: 183–191PubMedCrossRefGoogle Scholar
  21. Yang Y-C, Rabson M, Howley PM (1985) Dissociation of bovine papillomavirus transforming and transactivating functions. Nature 318: 575–577PubMedCrossRefGoogle Scholar

Copyright information

© Springer-Verlag Berlin · Heidelberg 1989

Authors and Affiliations

  • B. H. Horwitz
    • 1
  • J. Settleman
    • 1
  • S. S. Prakash
    • 1
  • D. DiMaio
    • 1
  1. 1.Department of Human GeneticsYale University School of MedicineNew HavenUSA

Personalised recommendations