Cyclin A and the retinoblastoma gene product complex with a common transcription factor (original) (raw)

Nature volume 352, pages 249–251 (1991)Cite this article

Abstract

THE retinoblastoma gene (Rb) product is a negative regulator of cellular proliferation1, an effect that could be mediated in part at the transcriptional level through its ability to complex with the sequence-specific transcription factor DRTF1 (ref. 2). This interac­tion is modulated by adenovirus El a, which sequesters the Rb protein3 and several other cellular proteins<3>, including cyclin A (refs 4, 5), a molecule that undergoes cyclical accumulation and destruction during each cell cycle6, 7 and which is required for cell cycle progression8. Cyclin A, which also complexes with DRTF1, facilitates the efficient assembly of the Rb protein into the complex. This suggests a role for cyclin A in regulating transcription and defines a transcription factor through which molecules that regu­late the cell cycle in a negative fashion, such as Rb, and in a positive fashion, such as cyclin A, interact. Mutant loss-of-function Rb alleles, which occur in a variety of tumour cells, also fail to complex with Ela and large T antigen9, 10. Here we report on a naturally occurring loss-of-function Rb allele encoding a protein that fails to complex with DRTF1. This might explain how mutation in the Rb gene prevents negative growth control.

This is a preview of subscription content, access via your institution

Access options

Subscribe to this journal

Receive 51 print issues and online access

$199.00 per year

only $3.90 per issue

Buy this article

Prices may be subject to local taxes which are calculated during checkout

Additional access options:

Similar content being viewed by others

References

  1. Marshall, C. J. Cell 64, 313–326 (1991).
    Article CAS Google Scholar
  2. Bandara, L. R. & La Thangue, N. B. Nature 351, 494–497 (1991).
    Article ADS CAS Google Scholar
  3. Whyte, P. et al. Nature 334, 124–129 (1988).
    Article ADS CAS Google Scholar
  4. Giordano, A. et al. Cell 58, 981–990 (1989).
    Article CAS Google Scholar
  5. Pines, J. & Hunter, T. Nature 346, 760–763 (1990).
    Article ADS CAS Google Scholar
  6. Evans, T., Rosenthal, E. T., Youngblom, J., Distel, D. & Hunt, T. Cell 33, 389–396 (1983).
    Article CAS Google Scholar
  7. Gautier, J. et al. Cell 60, 487–494 (1990).
    Article CAS Google Scholar
  8. Lehner, C. F. & O'Farrell, P. H. Cell 61, 535–547 (1990).
    Article CAS Google Scholar
  9. Hu, Q., Dyson, N. & Harlow, E. EMBO J. 9, 1147–1155 (1990).
    Article CAS Google Scholar
  10. Huang, H.-J. S., Wang, N. P., Tseng, B. Y., Lee, W. H. & Lee, E. Y.-H. P. EMBO J. 9, 1815–1822 (1990).
    Article CAS Google Scholar
  11. Lillie, J. W., Lowenstein, P. M., Green, M. R. & Green, M. Cell 50, 1091–1100 (1987).
    Article CAS Google Scholar
  12. Shivji, M. K. & La Thangue, N. B. Molec. cell. Biol. 11, 1686–1695 (1991).
    Article CAS Google Scholar
  13. Harlow, E., Whyte, P., Franza, B. R. & Schley, C. Molec. cell. Biol. 6, 1579–1589 (1986).
    Article CAS Google Scholar
  14. 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
  15. Friend, S. H. et al. Proc. natn. Acad. Sci. U.S.A. 84, 9059–9063 (1987).
    Article ADS CAS Google Scholar
  16. Lin, B. T.-Y., Gruenwald, S., Moria, A. O., Lee, W.-H. & Wang, J. Y. J. EMBO J. 10, 857–864 (1991).
    Article CAS Google Scholar
  17. Buchkovich, K., Duffy, L. A. & Harlow, E. Cell 58, 1097–1105 (1989).
    Article CAS Google Scholar
  18. Ludlow, J. W., Shon, J. Pipas, J. M., Livingston, D. M. & DeCaprio, J. A. Cell 60, 387–396 (1990).
    Article CAS Google Scholar
  19. Ludlow, J. W. et al. Cell 56, 57–65 (1989).
    Article CAS Google Scholar
  20. La Thangue, N. B., Thimmappaya, B. & Rigby, P. W. J. Nucleic Acids Res. 18, 2929–2938 (1990).
    Article CAS Google Scholar
  21. Kaelin, W. G., Pallas, D. C., DeCaprio, J. A., Kaye, F. J. & Livingston, D. M. Cell 64, 521–523 (1990).
    Article Google Scholar
  22. Smith, D. B. & Johnson, K. S. Gene 67, 31–40 (1988).
    Article CAS Google Scholar

Download references

Author information

Authors and Affiliations

  1. Laboratory of Eukaryotic Molecular Genetics, MRC National Institute for Medical Research, The Ridgeway, Mill Hill, London, NW7 1AA, UK
    Lasantha R. Bandara, Jörg P. Adamczewski, Tim Hunt & Nicholas B. La Thangue
  2. Imperial Cancer Research Fund, Clare Hall Laboratories, Blanche Lane, South Mimms, Potters Bar, Herts, EN6 3LD, UK
    Jörg P. Adamczewski & Tim Hunt

Authors

  1. Lasantha R. Bandara
    You can also search for this author inPubMed Google Scholar
  2. Jörg P. Adamczewski
    You can also search for this author inPubMed Google Scholar
  3. Tim Hunt
    You can also search for this author inPubMed Google Scholar
  4. Nicholas B. La Thangue
    You can also search for this author inPubMed Google Scholar

Rights and permissions

About this article

Cite this article

Bandara, L., Adamczewski, J., Hunt, T. et al. Cyclin A and the retinoblastoma gene product complex with a common transcription factor.Nature 352, 249–251 (1991). https://doi.org/10.1038/352249a0

Download citation

This article is cited by