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.

p21 is a universal inhibitor of cyclin kinases

Abstract

DEREGULATION of cell proliferation is a hallmark of neoplastic transformation. Alteration in growth control pathways must translate into changes in the cell-cycle regulatory machinery, but the mechanism by which this occurs is largely unknown. Compared with normal human fibroblasts, cells transformed with a variety of viral oncoproteins show striking changes in the subunit composition of the cyclin-dependent kinases (CDKs)1. In normal cells, CDKs exist predominantly in multiple quaternary complexes, each containing a CDK, cyclin, proliferating cell nuclear antigen and the p21 protein. However, in many transformed cells, proliferating cell nuclear antigen and p21 are lost from these multiprotein enzymes. Here we have investigated the significance of this phenomenon by molecular cloning of p21 and in vitro reconstitution of the quaternary cell-cycle kinase complexes. We find that p21 inhibits the activity of each member of the cyclin/CDK family. Furthermore, over expression of p21 inhibits the proliferation of mammalian cells. Our results indicate that p21 may be a universal inhibitor of cyclin kinases.

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

Relevant articles

Open Access articles citing this article.

Access options

Rent or buy this article

Prices vary by article type

from$1.95

to$39.95

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

References

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

    Article  CAS  Google Scholar 

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

    Article  CAS  Google Scholar 

  3. Draetta, G. Trends biochem. Sci. 15, 378–383 (1990).

    Article  CAS  Google Scholar 

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

    Article  CAS  Google Scholar 

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

    Article  CAS  Google Scholar 

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

    Article  CAS  Google Scholar 

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

    Article  CAS  Google Scholar 

  8. Kastan, M. B. et al. Cell 71, 587–597 (1992).

    Article  CAS  Google Scholar 

  9. Kawasaki, H., Emori, Y. & Suzuki, K. Analyt. Biochem. 191, 332–336 (1990).

    Article  CAS  Google Scholar 

  10. Xiong, Y., Menninger, J., Beach, D. & Ward, D. Genomics 13, 575–584 (1992).

    Article  CAS  Google Scholar 

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

    Article  CAS  Google Scholar 

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

    Article  CAS  Google Scholar 

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

    Article  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Rights and permissions

Reprints and Permissions

About this article

Cite this article

Xiong, Y., Hannon, G., Zhang, H. et al. p21 is a universal inhibitor of cyclin kinases. Nature 366, 701–704 (1993). https://doi.org/10.1038/366701a0

Download citation

  • Received:

  • Accepted:

  • Issue Date:

  • DOI: https://doi.org/10.1038/366701a0

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

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