Abstract
Early gene E5 of bovine papillomavirus type 1 encodes a 44-amino-acid protein whose expression can transform immortalized mouse cell lines. We have previously reported that a chemically synthesized E5 peptide functions to induce cellular DNA synthesis upon microinjection into growth-arrested mouse cells. We further defined the two E5 domains essential for the full DNA synthesis induction activity by the analysis of E5 deletion and amino acid substitution mutant peptides. The first domain is the C-terminal 13-amino-acid core which is sufficient to activate DNA synthesis at high peptide concentration and contains two essential, highly conserved cysteine residues. The second domain is the 7-amino-acid hydrophobic sequence contiguous to the core domain which is sufficient to confer a 1,000-fold higher molar specific activity to the E5 peptide. A random hydrophobic sequence, but not charged amino acids, fulfills the function of the second domain.
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Selected References
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- Bubb V., McCance D. J., Schlegel R. DNA sequence of the HPV-16 E5 ORF and the structural conservation of its encoded protein. Virology. 1988 Mar;163(1):243–246. doi: 10.1016/0042-6822(88)90259-0. [DOI] [PubMed] [Google Scholar]
- Burkhardt A., DiMaio D., Schlegel R. Genetic and biochemical definition of the bovine papillomavirus E5 transforming protein. EMBO J. 1987 Aug;6(8):2381–2385. doi: 10.1002/j.1460-2075.1987.tb02515.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Burkhardt A., Willingham M., Gay C., Jeang K. T., Schlegel R. The E5 oncoprotein of bovine papillomavirus is oriented asymmetrically in Golgi and plasma membranes. Virology. 1989 May;170(1):334–339. doi: 10.1016/0042-6822(89)90391-7. [DOI] [PubMed] [Google Scholar]
- DiMaio D., Guralski D., Schiller J. T. Translation of open reading frame E5 of bovine papillomavirus is required for its transforming activity. Proc Natl Acad Sci U S A. 1986 Mar;83(6):1797–1801. doi: 10.1073/pnas.83.6.1797. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Gluzman Y., Sambrook J. F., Frisque R. J. Expression of early genes of origin-defective mutants of simian virus 40. Proc Natl Acad Sci U S A. 1980 Jul;77(7):3898–3902. doi: 10.1073/pnas.77.7.3898. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Green M., Loewenstein P. M. Demonstration that a chemically synthesized BPV1 oncoprotein and its C-terminal domain function to induce cellular DNA synthesis. Cell. 1987 Dec 4;51(5):795–802. doi: 10.1016/0092-8674(87)90102-4. [DOI] [PubMed] [Google Scholar]
- Groff D. E., Lancaster W. D. Molecular cloning and nucleotide sequence of deer papillomavirus. J Virol. 1985 Oct;56(1):85–91. doi: 10.1128/jvi.56.1.85-91.1985. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Halbert C. L., Galloway D. A. Identification of the E5 open reading frame of human papillomavirus type 16. J Virol. 1988 Mar;62(3):1071–1075. doi: 10.1128/jvi.62.3.1071-1075.1988. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Horwitz B. H., Burkhardt A. L., Schlegel R., DiMaio D. 44-amino-acid E5 transforming protein of bovine papillomavirus requires a hydrophobic core and specific carboxyl-terminal amino acids. Mol Cell Biol. 1988 Oct;8(10):4071–4078. doi: 10.1128/mcb.8.10.4071. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Moreno-Lopez J., Ahola H., Eriksson A., Bergman P., Pettersson U. Reindeer papillomavirus transforming properties correlate with a highly conserved E5 region. J Virol. 1987 Nov;61(11):3394–3400. doi: 10.1128/jvi.61.11.3394-3400.1987. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Nakabayashi Y., Chattopadhyay S. K., Lowy D. R. The transforming function of bovine papillomavirus DNA. Proc Natl Acad Sci U S A. 1983 Oct;80(19):5832–5836. doi: 10.1073/pnas.80.19.5832. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Schiller J. T., Vass W. C., Lowy D. R. Identification of a second transforming region in bovine papillomavirus DNA. Proc Natl Acad Sci U S A. 1984 Dec;81(24):7880–7884. doi: 10.1073/pnas.81.24.7880. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Schiller J. T., Vass W. C., Vousden K. H., Lowy D. R. E5 open reading frame of bovine papillomavirus type 1 encodes a transforming gene. J Virol. 1986 Jan;57(1):1–6. doi: 10.1128/jvi.57.1.1-6.1986. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Schlegel R., Wade-Glass M., Rabson M. S., Yang Y. C. The E5 transforming gene of bovine papillomavirus encodes a small, hydrophobic polypeptide. Science. 1986 Jul 25;233(4762):464–467. doi: 10.1126/science.3014660. [DOI] [PubMed] [Google Scholar]
- Yang Y. C., Okayama H., Howley P. M. Bovine papillomavirus contains multiple transforming genes. Proc Natl Acad Sci U S A. 1985 Feb;82(4):1030–1034. doi: 10.1073/pnas.82.4.1030. [DOI] [PMC free article] [PubMed] [Google Scholar]