Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Letter
  • Published:

A new regulatory motif in cell-cycle control causing specific inhibition of cyclin D/CDK4

Nature volume 366, pages 704–707 (1993)Cite this article

Abstract

THE division cycle of eukaryotic cells is regulated by a family of protein kinases known as the cyclin-dependent kinases (CDKs)1,2. The sequential activation of individual members of this family and their consequent phosphorylation of critical substrates promotes orderly progression through the cell cycle3,4. The complexes formed by CDK4 and the D-type cyclins have been strongly implicated in the control of cell proliferation during the G1 phase3–6. CDK4 exists, in part, as a multi-protein complex with a D-type cyclin, proliferating cell nuclear antigen and a protein, p21 (refs 7–9). CDK4 associates separately with a protein of Mr 16K, particularly in cells lacking a functional retinoblastoma protein9. Here we report the isolation of a human p16 complementary DNA and demonstrate that p16 binds to CDK4 and inhibits the catalytic activity of the CDK4/cyclin D enzymes. p16 seems to act in a regulatory feedback circuit with CDK4, D-type cyclins and retinoblastoma protein.

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

Access options

Buy this article

  • Purchase on Springer Link
  • Instant access to full article PDF
Buy now

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

Similar content being viewed by others

References

  1. Solomon, M., J. Curr. Opin. Cell Biol. 5, 180–186 (1993).

    Article  CAS  Google Scholar 

  2. Nigg, E. A. Curr. Opin. Cell Biol. 5, 187–193 (1993).

    Article  CAS  Google Scholar 

  3. Motokura, T. & Arnold, A. Biochim. biophys. Acta 1155, 63–78 (1993).

    CAS  PubMed  Google Scholar 

  4. Sherr, C. J. Cell 73, 1059–1065 (1993).

    Article  CAS  Google Scholar 

  5. Matsushime, H., Roussel, M. F., Ashmun, R. A. & Sherr, C. J. Cell 65, 701–713 (1991).

    Article  CAS  Google Scholar 

  6. Matsushime, H. et al. Cell 71, 323–334 (1992).

    Article  CAS  Google Scholar 

  7. Xiong, Y., Shang, H. & Beach, D. Cell 71, 505–514 (1992).

    Article  CAS  Google Scholar 

  8. Zhang, H., Xiong, Y. & Beach, D. Molec. biol. Cell 4, 897–906 (1993).

    Article  CAS  Google Scholar 

  9. Xiong, Y., Zhang, H. & Beach, D. Genes Dev. 7, 1572–1583 (1993).

    Article  CAS  Google Scholar 

  10. Fields, S. & Song, O. Nature 340, 245–246 (1989).

    Article  ADS  CAS  Google Scholar 

  11. Meyerson, M. et al. EMBO J. 11, 2909–2917 (1992).

    Article  CAS  Google Scholar 

  12. Kato, J.-Y., Matsushime, H., Hiebert, S. W., Ewen, M. E. & Sherr, C. J. Genes Dev. 7, 331–342 (1993).

    Article  CAS  Google Scholar 

  13. Ewen, M. E. et al. Cell 73, 487–497 (1993).

    Article  CAS  Google Scholar 

  14. Zhu, L. et al. Genes Dev. 7, 1111–1125 (1993).

    Article  CAS  Google Scholar 

  15. Hannon, G. J., Demetrick, D. & Beach, D. Genes Dev. 7, 2378–2391 (1993).

    Article  CAS  Google Scholar 

  16. Li, Y., Graham, C., Lacy, S., Duncan, A. M. V. & Whyte, P. Genes Dev. 7, 2366–2377 (1993).

    Article  CAS  Google Scholar 

  17. Lukas, J., Pagano, M., Staskova, Z., Draetta, G. & Bartek, J. Oncogene (in the press).

  18. Xiong, Y. et al. Nature 366, 701–704 (1993).

    Article  ADS  CAS  Google Scholar 

  19. Lees, E. M. & Harlow, E. Molec. cell. Biol. 13, 1194–1201 (1993).

    Article  CAS  Google Scholar 

  20. Zheng, X.-F. & Ruderman, J. V. Cell 75, 155–164 (1993).

    Article  CAS  Google Scholar 

  21. Michaely, P. & Bennet, V. Trends Cell Biol. 2, 127–129 (1992).

    Article  CAS  Google Scholar 

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

    Google Scholar 

  23. Chen, X.-S., Brash, A. R. & Funk, C. D. Eur. J. Biochem. 214, 845–852 (1993).

    Article  CAS  Google Scholar 

Download references

Author information

Author notes

  1. David Beach: To whom correspondence should be addressed.

Authors and Affiliations

  1. Howard Hughes Medical Institute, Cold Spring Harbor Laboratory, PO Box 100, Cold Spring Harbor, New York, 11724, USA

    Manual Serrano, Gregory J. Hannon & David Beach

Authors
  1. Manual Serrano
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Gregory J. Hannon
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. David Beach
    View author publications

    You can also search for this author in PubMed Google Scholar

Rights and permissions

Reprints and permissions

About this article

Cite this article

Serrano, M., Hannon, G. & Beach, D. A new regulatory motif in cell-cycle control causing specific inhibition of cyclin D/CDK4. Nature 366, 704–707 (1993). https://doi.org/10.1038/366704a0

Download citation

  • Received:

  • Accepted:

  • Issue Date:

  • DOI: https://doi.org/10.1038/366704a0

This article is cited by

Comments

By submitting a comment you agree to abide by our Terms and Community Guidelines. If you find something abusive or that does not comply with our terms or guidelines please flag it as inappropriate.

Search

Advanced search

Quick links

Nature Briefing

Sign up for the Nature Briefing newsletter — what matters in science, free to your inbox daily.

Get the most important science stories of the day, free in your inbox. Sign up for Nature Briefing