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.
Subscribe to Journal
Get full journal access for 1 year
only $3.90 per issue
All prices are NET prices.
VAT will be added later in the checkout.
Rent or Buy article
Get time limited or full article access on ReadCube.
All prices are NET prices.
Xiong, Y., Zhang, H. & Beach, D. Genes Dev. 7, 1572–1583 (1993).
Sherr, C. Cell 73, 1059–1065 (1993).
Draetta, G. Trends biochem. Sci. 15, 378–383 (1990).
Xiong, Y., Zhang, H. & Beach, D. Cell 71, 505–514 (1992).
Zhang, H., Xiong, Y. & Beach, D. Molec. Biol. Cell 4, 897–906 (1993).
Matsushime, H. et al. Cell 71, 323–334 (1992).
Zhu, L. et al. Genes Dev. 7, 1111–1125 (1993).
Kastan, M. B. et al. Cell 71, 587–597 (1992).
Kawasaki, H., Emori, Y. & Suzuki, K. Analyt. Biochem. 191, 332–336 (1990).
Xiong, Y., Menninger, J., Beach, D. & Ward, D. Genomics 13, 575–584 (1992).
Hannon, G. J., Demetrick, D. & Beach, D. Genes Dev. 7, 2378–2391 (1993).
Draetta, G. & Beach, D. Cell 54, 17–26 (1988).
Ewen, M. E. et al. Cell 73, 487–497 (1993).
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) doi:10.1038/366701a0
Cyclin-dependent kinase 2 (Cdk-2) from the White shrimp Litopenaeus vannamei: Molecular characterization and tissue-specific expression during hypoxia and reoxygenation
Comparative Biochemistry and Physiology Part A: Molecular & Integrative Physiology (2019)
Effect of Hepatitis Viruses on the Nrf2/Keap1-Signaling Pathway and Its Impact on Viral Replication and Pathogenesis
International Journal of Molecular Sciences (2019)
Ginsenoside Rk1 induces cell death through ROS-mediated PTEN/PI3K/Akt/mTOR signaling pathway in MCF-7 cells
Journal of Functional Foods (2019)