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Independent binding of the retinoblastoma protein and p107 to the transcription factor E2F

Abstract

THE cellular protein p107 and the retinoblastoma protein (pRB) have many features in common. Most strikingly, they contain homologous protein domains that mediate interaction with the oncoproteins of several small DNA tumour viruses, including adenovirus El A and SV40 large-T antigen1–9. In cells that do not contain these viral oncoproteins, pRB interacts with the cellular transcription factor E2F (refs 10–12) or a related protein termed DRTF1 (ref. 13). E2F associates with a form of pRB that is found primarily in Gl cells10. It seems that the E2F-pRB complex dissociates near the Gl-S boundary before the initiation of S phase, releasing free E2F and apparently stimulating the ability of E2F to activate transcription14. Cells that express E1A have no or little pRB-E2F complex, presumably because of the association of E1A with pRB10–15. During S phase, E2F forms a second complex that contains cyclin A but apparently lacks pRB15. Here, we report that p107 is found in the cyclin A/E2F complex and that this complex also contains p33cdk2. These observations suggest that p107 and pRB cooperate in the regulation of E2F activity, each affecting different stages of the cell cycle. Thus, by binding to pRB and pi 07, El A and large-T antigen target two distinct aspects of E2F regulation.

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References

  1. Whyte, P. et al. Nature 334, 124–129 (1988).

    Article  ADS  CAS  PubMed  Google Scholar 

  2. DeCaprio, J. A. et al. Cell 54, 275–283 (1988).

    Article  CAS  PubMed  Google Scholar 

  3. Whyte, P., Williamson, N. M. & Harlow, E. Cell 56, 67–75 (1989).

    Article  CAS  PubMed  Google Scholar 

  4. Dyson, N., Buchkovich, K., Whyte, P. & Harlow, E. Cell 58, 249–255 (1989).

    Article  CAS  PubMed  Google Scholar 

  5. Ewen, M. E. et al. Cell 58, 257–267 (1989).

    Article  CAS  PubMed  Google Scholar 

  6. Hu, Q., Dyson, N. & Harlow, E. EMBO J. 9, 1147–1155 (1990).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  7. Kaelin, W. G., Ewen, M. E. & Livingston, D. M. Molec. cell Biol. 10, 3761–3769 (1990).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  8. Huang, S. et al. EMBO J. 9, 1815–1822 (1990).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  9. Ewen, M. E., Xing, Y., Lawrence, J. B. & Livingston, D. M. Cell 66, 1155–1164 (1991).

    Article  CAS  PubMed  Google Scholar 

  10. Chellappan, S., Hiebert, S., Mudryj, M., Horowitz, J. M. & Nevins, J. R. Cell 65, 1053–1061 (1991).

    Article  CAS  PubMed  Google Scholar 

  11. Bagchi, S., Weinmann, R. & Raychauhuri, P. Cell 65, 1063–1072 (1991).

    Article  CAS  PubMed  Google Scholar 

  12. Chittendon, T., Livingston, D. M. & Kaelin, W. G. Cell 65, 1073–1082 (1991).

    Article  Google Scholar 

  13. Bandara, L. & La Thangue, N. Nature 351, 494–497 (1991).

    Article  ADS  CAS  PubMed  Google Scholar 

  14. Hiebert, S. W., Chellappan, S. P., Horowitz, J. M. & Nevins, J. R. Genes Dev. (in the press).

  15. Mudryj, M. et al. Cell 65, 1243–1251 (1991).

    Article  CAS  PubMed  Google Scholar 

  16. Faha, B., Ewen, M. E., Tsai, L.-H., Livingston, D. M. & Harlow, E. Science (in the press).

  17. Ewen, M. E., Faha, B., Harlow, E. & Livingston, D. M. Science (in the press).

  18. Shew, J-Y. et al. Proc. natn. Acad. Sci. U.S.A. 87, 6–10 (1990).

    Article  ADS  CAS  Google Scholar 

  19. Giordano, A. et al. Cell 58, 981–990, (1989).

    Article  CAS  PubMed  Google Scholar 

  20. Pines, J. & Hunter, T. Nature 346, 760–763 (1990).

    Article  ADS  CAS  PubMed  Google Scholar 

  21. Giordano, A. et al. Science 253, 1271–1275 (1991).

    Article  ADS  CAS  PubMed  Google Scholar 

  22. Tsai, L.-H., Harlow, E. & Meyerson, M. Nature 353, 174–177 (1991).

    Article  ADS  CAS  PubMed  Google Scholar 

  23. Mudryj, M., Hiebert, S. W. & Nevins, J. R. EMBO J. 7, 2179–2184 (1990).

    Article  Google Scholar 

  24. Hu, Q. et al. Molec. cell. Biol. 11, 5792–5799 (1991).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  25. Harlow, E., Franza, B. R. Jr & Schley, C. J. Virol. 55, 533–546 (1985).

    CAS  PubMed  PubMed Central  Google Scholar 

  26. Harlow, E., Crawford, L., Pim, D. & Williamson, N. J. Virol. 39, 861–869 (1981).

    CAS  PubMed  PubMed Central  Google Scholar 

  27. Krieg, P. A. & Melton, D. A. Nucleic Acids Res. 12, 7057–7070 (1984).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  28. Laemmli, U. K. Nature 227, 681–685 (1970).

    Article  ADS  Google Scholar 

  29. Bonner, W. M. & Laskey, R. A. Eur. J. Biochem. 46, 83–88 (1974).

    Article  CAS  PubMed  Google Scholar 

  30. Cleveland, D. W., Fischer, S. G., Kirschner, M. W. & Laemmli, U. K. J. biol. Chem. 252, 1102–1106 (1977).

    CAS  PubMed  Google Scholar 

  31. Towbin, H., Staehelin, T. & Gordon, J. Proc. natn. Acad. Sci. U.S.A. 76, 4350–4354 (1979).

    Article  ADS  CAS  Google Scholar 

  32. Harlow, E. & Lane, D. Antibodies: A Laboratory Manual (Cold Spring Harbor Laboratory Press, New York, 1988).

    Google Scholar 

  33. Kaelin, W. G. et al. Cell 64, 521–532 (1991).

    Article  CAS  PubMed  Google Scholar 

  34. Draetta, G. & Beach, D. Cell 54, 17–26 (1988).

    Article  CAS  PubMed  Google Scholar 

  35. Meyerson, M., Faha, B., Harlow, E. & Tsai, L.-H. Cold Spring Harb. Symp. quant. Biol. 58, (in the press).

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Cao, L., Faha, B., Dembski, M. et al. Independent binding of the retinoblastoma protein and p107 to the transcription factor E2F. Nature 355, 176–179 (1992). https://doi.org/10.1038/355176a0

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