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Mechanism of active transcriptional repression by the retinoblastoma protein

Nature volume 375, pages 812–816 (1995)Cite this article

Abstract

THE retinoblastoma tumour-suppressor protein (Rb) belongs to a family that share a motif known as the pocket. The pocket was originally identified as the region of Rb required for binding to oncoproteins from DNA tumour viruses1,2, which disrupt the binding of Rb to the E2F family of cell-cycle transcription factors (referred to collectively here as E2F)3. Rb switches E2F sites from positive to negative elements4, suggesting that Rb–E2F is an active complex that blocks transcription. Here we report that Rb is selectively recruited to promoters through E2F, where it in turn inactivates surrounding transcription factors by blocking their interaction with the basal transcription complex. We suggest that this represser activity is essential for inhibiting promoters that contain enhancers in addition to E2F sites.

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References

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

    Article  CAS  Google Scholar 

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

    Article  CAS  Google Scholar 

  3. Bagchi, S., Raychaudhuri, P. & Nevins, J. R. Cell 62, 659–669 (1990).

    Article  CAS  Google Scholar 

  4. Weintraub, S. J., Prater, C. A. & Dean, D. C. Nature 358, 259–261 (1992).

    Article  ADS  CAS  Google Scholar 

  5. Scheffner, M., Munger, K., Byrne, J. C. & Howley, P. M. Proc. natn. Acad. Sci. U.S.A. 88, 5523–5527 (1991).

    Article  ADS  CAS  Google Scholar 

  6. Kaye, F. J., Kratzke, R. A., Gerster, J. L. & Horowitz, J. M. Proc. natn. Acad. Sci. U.S.A. 87, 6922–6926 (1990).

    Article  ADS  CAS  Google Scholar 

  7. Qian, Y., Luckey, C., Horton, L., Esser, M. & Templeton, D. J. Molec. cell. Biol. 12, 5363–5372 (1992).

    Article  CAS  Google Scholar 

  8. Chen, P. L., Scully, P., Shew, J. Y., Wang, J. Y. & Lee, W. H. Cell 58, 1193–1198 (1989).

    Article  CAS  Google Scholar 

  9. DeCaprio, J. A. et al. Cell 58, 1085–1095 (1989).

    Article  CAS  Google Scholar 

  10. Hinds, P. W. et al. Cell 70, 993–1006 (1992).

    Article  CAS  Google Scholar 

  11. Chittenden, T., Livingston, D. M. & Kaelin, W. Jr Cell 65, 1073–1082 (1991).

    Article  CAS  Google Scholar 

  12. Hagemeier, C., Bannister, A. J., Cook, A. & Kouzarides, T. Proc. natn. Acad. Sci. U.S.A. 90, 1580–1584 (1993).

    Article  ADS  CAS  Google Scholar 

  13. Wang, C. Y., Petryniak, B., Thompson, C. B., Kaelin, W. G. & Leiden, J. M. Science 260, 1330–1335 (1993).

    Article  ADS  CAS  Google Scholar 

  14. Hateboer, G. et al. Proc. natn. Acad. Sci. U.S.A. 90, 8489–8493 (1993).

    Article  ADS  CAS  Google Scholar 

  15. Martin, K. J., Lillie, J. W. & Green, M. R. Nature 346, 147–152 (1990).

    Article  ADS  CAS  Google Scholar 

  16. Girling, R. et al. Nature 362, 83–87 (1993).

    Article  ADS  CAS  Google Scholar 

  17. Hagemeier, C., Cook, A. & Kouzarides, T. Nucleic Acids Res. 21, 4998–5004 (1993).

    Article  CAS  Google Scholar 

  18. Kashanchi, F. et al. Nature 367, 295–299 (1994).

    Article  ADS  CAS  Google Scholar 

  19. Iademarco, M. F., McQuillan, J. J., Rosen, G. D. & Dean, D. C. J. biol. Chem. 267, 16323–16329 (1992).

    CAS  PubMed  Google Scholar 

  20. Kaelin, W. Jr, Pallas, D. C., DeCaprio, J. A., Kaye, F. J. & Livingston, D. M. Cell 64, 521–532 (1991).

    Article  CAS  Google Scholar 

  21. Helin, K. et al. Genes Dev. 7, 1850–1861 (1993).

    Article  CAS  Google Scholar 

  22. Sadowski, I., Bell, B., Broad, P. & Hollis, M. Gene 118, 137–141 (1992).

    Article  CAS  Google Scholar 

  23. Kato, G. J., Barrett, J., Villa-Garcia, M. & Dang, C. V. Molec. cell. Biol. 10, 5914–5920 (1990).

    Article  CAS  Google Scholar 

  24. Sadowski, I., Ma, J., Triezenberg, S. & Ptashne, M. Nature 335, 563–564 (1988).

    Article  ADS  CAS  Google Scholar 

  25. Seipel, K., Georgiev, O. & Schaffner, W. EMBO J. 11, 4961–4968 (1992).

    Article  CAS  Google Scholar 

  26. Tanese, N., Pugh, B. F. & Tjian, R. Genes Dev. 5, 2212–2224 (1991).

    Article  CAS  Google Scholar 

  27. Smith, D. B. & Johnson, K. S. Gene 67, 31–40 (1988).

    Article  CAS  Google Scholar 

  28. Chiang, C.-M. & Roeder, R. G. Science 267, 531–536 (1995).

    Article  ADS  CAS  Google Scholar 

  29. Dowdy, S. F. et al. Cell 73, 499–511 (1993).

    Article  CAS  Google Scholar 

Download references

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Authors and Affiliations

  1. Departments of Medicine and Cell Biology, Washington University School of Medicine, St Louis, Missouri, 63110, USA

    Steven J. Weintraub, Kevin N. B. Chow, Robin X. Luo, Steven H. Zhang, Song He & Douglas C. Dean

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  1. Steven J. Weintraub
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  2. Kevin N. B. Chow
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  3. Robin X. Luo
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  4. Steven H. Zhang
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  6. Douglas C. Dean
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Weintraub, S., Chow, K., Luo, R. et al. Mechanism of active transcriptional repression by the retinoblastoma protein. Nature 375, 812–816 (1995). https://doi.org/10.1038/375812a0

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