Abstract
THE E7 transforming protein of human papilloma virus-16 binds to the retinoblastoma gene product (pRb)1, 2 through a nine-amino-acid segment of E7 (21–29)3–5. This segment of E7 is homologous to the pRb-binding domains of the simian virus 40 large T and adenovirus El A transforming proteins6–9. Each of these viral transá-forming proteins bind to the same region of pRb10, 11. To isolate cellular proteins that interact with this viral protein-binding domain on pRb12, 13, we used recombinant pRb to screen a human complementary DNA expression library. Two cDNAs were isolated that encode retinoblastoma binding proteins (RBP-1 and RBP-2). We report here that these RBP genes exist in separate loci and produce discrete messenger RNAs. The predicted amino-acid sequence of these genes showed no homology to known proteins, but both RBPs contain the pRb binding motif conserved between E7, large T and E1A14. In vitro expression of the RBP cDNAs yielded proteins that specifically bound to pRb. Recombinant E7 protein, the E7 21–29 peptide and the homologous RBP-1 peptide inhibited RBP-pRb binding. Mutations introduced into the putaá-tive pRb-binding segment in RBP-1 impaired its binding activity. These studies indicate that the cellular RBP-1, RBP-2 and viral E7 proteins interact with pRb through similar domains.
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References
Friend, S. H. et al. Nature 323, 643–646 (1986).
Lee, W.-H. et al. Science 235, 1394–1399 (1987).
Dyson, N., Howley, P. M., Munger, K. & Harlow, E. Science 243, 934–937 (1989).
Phelps, W. C., Yee, C. L., Münger, K. & Howley, P. M. Cell 53, 539–547 (1988).
Jones, R. E. et al. J. biol. Chem. 265, 12782–12785 (1990).
Moran, E. Nature 334, 168–170 (1988).
DeCaprio, J. A. et al. Cell 54, 275–283 (1988).
Whyte, P. et al. Nature 334, 124–129 (1988).
Dyson, N., Buchkovich, K., Whyte, P. & Harlow, E. Cell 58, 249–255 (1989).
Kaelin, W. G. Jr, Ewen, M. E. & Livingston, D. M. Molec. cell. Biol. 10, 3761–3769 (1990).
Hu, Q., Dyson, N. & Harlow, E. EMBO J. 9, 1147–1155 (1990).
Kaelin, W. G. Jr, Pallas, D. C., DeCaprio, J. A., Kaye, F. J. & Livingston, D. M. Cell 64, 521–532 (1991).
Huang, S., Lee, W.-H., Lee, E. Y.-H. Nature 350, 160–162 (1991).
Figge, J., Webster, T., Smith, T. F. & Paucha, E. J. Virol. 62, 1814–1818 (1988).
Macgregor, P. F., Abste, C. & Curran, T. Oncogene 5, 451–458 (1990).
Young, R. A. & Davis, R. W. Proc. natn. Acad. Sci. U.S.A. 80, 1194–1198 (1983).
Sanger, F., Nicklen, S. & Coulson, A. R. Proc. natn. Acad. Sci. U.S.A. 74, 5463–5467 (1977).
Huynh, T. U., Young, R. & Davis, R. W. in DNA Cloning Techniques: A Practical Approach (ed. Glober, D.) (IRL Press, Oxford, 1985).
Devereux, J., Haeberli, P. & Smithies, O. Nucleic Acids Res. 12, 387–395 (1984).
Smith, D. B. & Johnson, K. S. Gene 67, 31–40 (1988).
Münger, K. et al. EMBO J. 8, 4099–4105 (1989).
Edmonds, C. & Vousden, K. H. J. Virol. 63, 2650–2656 (1989).
Barbosa, M. S. et al. EMBO J. 9, 153–160 (1990).
Watanabe, S., Kanda, T., Sato, H., Furuno, A. & Yoshiike, K. J. Virol. 64, 207–214 (1990).
Sambrook, J., Fritsch, E. F. & Maniatis, T. in Molecular Cloning, A Laboratory Manual 2nd edn (CSH Press, New York, 1989).
Whyte, P., Williamson, N. M. & Harlow, E. Cell 56, 67–75 (1989).
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Defeo-Jones, D., Huang, P., Jones, R. et al. Cloning of cDNAs for cellular proteins that bind to the retinoblastoma gene product. Nature 352, 251–254 (1991). https://doi.org/10.1038/352251a0
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DOI: https://doi.org/10.1038/352251a0
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