Separate domains of p21 involved in the inhibition of Cdk kinase and PCNA (original) (raw)

Nature volume 374, pages 386–388 (1995)Cite this article

Abstract

THE protein p21 (WAF1, CIP1 or sdil), induced by the tumour-suppressor protein p53, interacts with and inhibits two different targets essential for cell-cycle progression1–8. One of these is the cyclin–Cdk family of kinases and the other is the essential DNA replication factor, proliferating-cell nuclear antigen (PCNA). We report here that separate domains of p21 are responsible for interacting with and inhibiting the two targets. An amino-terminal domain inhibits cyclin–Cdk kinases and a carboxyl-terminal domain inhibits PCNA. Using these separated domains, we have determined that p21 inhibits different biological systems through different targets. The PCNA-binding domain is sufficient for inhibition of DNA replication based on simian virus 40, whereas the Cdk2-binding domain is sufficient for inhibition of DNA replication based on Xenopus egg extract and for growth suppression in transformed human cells.

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Authors and Affiliations

  1. Department of Pathology, Division of Molecular Oncology, Brigham and Women's Hospital, Harvard Medical School, 75 Francis Street, Boston, Massachusetts, 02115, USA
    Junjie Chen & Anindya Dutta
  2. Department of Cell Biology, Harvard Medical School, 25 Shattuck Street, Boston, Massachusetts, 02115, USA
    Peter K. Jackson & Marc W. Kirschner

Authors

  1. Junjie Chen
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  2. Peter K. Jackson
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  3. Marc W. Kirschner
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  4. Anindya Dutta
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Chen, J., Jackson, P., Kirschner, M. et al. Separate domains of p21 involved in the inhibition of Cdk kinase and PCNA.Nature 374, 386–388 (1995). https://doi.org/10.1038/374386a0

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