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p21 is a universal inhibitor of cyclin kinases

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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.

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Author notes

  1. Yue Xiong

    Present address: University of North Carolina, Chapel Hill, Room 214, Fordham Hall, Chapel Hill, North Carolina, 27599, USA

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

Authors and Affiliations

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

    Yue Xiong, Gregory J. Hannon, Hui Zhang, David Casso & David Beach

  2. Cold Spring Harbor Laboratory, 1, Bungtown Road, Cold Spring Harbor, New York, 11724, USA

    Yue Xiong, Gregory J. Hannon, Hui Zhang, David Casso, Ryuji Kobayashi & David Beach

Authors
  1. Yue Xiong
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  2. Gregory J. Hannon
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  3. Hui Zhang
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  4. David Casso
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  5. Ryuji Kobayashi
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  6. David Beach
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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

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

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