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A non-enzymatic p21 protein inhibitor of stress-activated protein kinases

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Abstract

THE stress-activated protein kinases (SAPKs), which are identical to the c-Jun amino-terminal kinases (JNKs), are activated in response to a variety of cellular stresses, including DNA damage, heat shock or tumour-necrosis factor-α1,2. SAPK, a subfamily of the mitogen-activated protein (MAP) kinases, is a major protein kinase that phosphorylates c-Jun and other transcription factors2–5. SAPK phosphorylation of transcription factors is important in stress-activated signalling cascades1–6. Here we report that the protein p21WAF1/CIP1/Sdil, a DNA-damage-inducible cell-cycle inhibitor7–10, acts as an inhibitor of the SAPK group of mammalian MAP kinases. This highlights a new biochemical activity of p21, which may provide the first evidence for a non-enzymatic inhibitory protein for SAPK. We suggest that p21, by inhibiting SAPK, may participate in regulating signalling cascades that are activated by cellular stresses such as DNA damage.

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References

  1. Kyriakis, J. M. et al. Nature 369, 156–160 (1994).

    Article  ADS  CAS  Google Scholar 

  2. Dérijard, B. et al. Cell 76, 1025–1037 (1994).

    Article  Google Scholar 

  3. Gupta, S., Campbell, D., Dérijard, B. & Davis, R. J. Science 267, 389–393 (1995).

    Article  ADS  CAS  Google Scholar 

  4. van Dam, H. et al. EMBO J. 14, 1798–1811 (1995).

    Article  CAS  Google Scholar 

  5. Whitmarsh, A. J., Shore, P., Sharrocks, A. D. & Davis, R. J. Science 269, 403–407 (1995).

    Article  ADS  CAS  Google Scholar 

  6. Davis, R. J. Trends biochem. Sci. 19, 470–473 (1994).

    Article  CAS  Google Scholar 

  7. EI-Deiry, W. S. et al. Cell 75, 817–825 (1993).

    Article  Google Scholar 

  8. Harper, J. W., Adami, G. R., Wei, N., Keyomarsi, K. & Elledge, S. J. Cell 75, 805–816 (1993).

    Article  CAS  Google Scholar 

  9. Noda, A., Ning, Y., Venable, S. F., Pereira, S. O. & Smith, J. R. Expl Cell Res. 211, 90–98 (1994).

    Article  CAS  Google Scholar 

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

    Article  ADS  CAS  Google Scholar 

  11. Han, J., Lee, J.-D., Bibbs, L. & Ulevitch, R. J. Science 265, 808–811 (1994).

    Article  ADS  CAS  Google Scholar 

  12. Chen, J., Jackson, P. K., Kirschner, M. W. & Dutta, A. Nature 374, 386–388 (1995).

    Article  ADS  CAS  Google Scholar 

  13. Nakanishi, M., Robetorye, R., Adami, G. R., Pereira-Smith, O. M. & Smith, J. R. EMBO J. 14, 555–563 (1995).

    Article  CAS  Google Scholar 

  14. Hunter, T. & Pines, J. Cell 79, 573–582 (1994).

    Article  CAS  Google Scholar 

  15. Serrano, M., Hannon, G. J. & Beach, D. Nature 366, 704–707 (1993).

    Article  ADS  CAS  Google Scholar 

  16. Fields, S. & Song, O. Nature 340, 245–247 (1989).

    Article  ADS  CAS  Google Scholar 

  17. Sánchez, I. et al. Nature 372, 794–798 (1994).

    Article  ADS  Google Scholar 

  18. Dérijard, B. et al. Science 267, 682–685 (1995).

    Article  ADS  Google Scholar 

  19. Lin, A. et al. Science 268, 286–290 (1995).

    Article  ADS  CAS  Google Scholar 

  20. Angel, P. & Karin, M. Biochim. biophys. Acta 1072, 129–157 (1991).

    CAS  Google Scholar 

  21. Herrlich, P., Ponta, H. & Rahmsdorf, H. J. Rev. Physiol. biochem. Pharmac. 119, 187–223 (1992).

    CAS  Google Scholar 

  22. Vogt, P. K. & Bos, T. S. Adv. Cancer Res. 55, 1–35 (1990).

    Article  CAS  Google Scholar 

  23. Hilberg, F. & Wagner, E. F. Oncogene 7, 2371–2380 (1992).

    CAS  Google Scholar 

  24. Ham, J. et al. Neuron 14, 927–939 (1995).

    Article  CAS  Google Scholar 

  25. Akashi, M. et al. J. biol. Chem. 270, 19181–19187 (1995).

    Article  CAS  Google Scholar 

  26. Osawa, Y. et al. Biochem. biophys. Res. Commun. 216, 429–437 (1995).

    Article  CAS  Google Scholar 

  27. Waga, S., Hannon, G. J., Beach, D. & Stillman, B. Nature 369, 574–578 (1994).

    Article  ADS  CAS  Google Scholar 

  28. Seger, R. & Krebs, E. G. FASEB J. 9, 726–735 (1995).

    Article  CAS  Google Scholar 

  29. Chen, C. & Okayama, H. Molec. cell. Biol. 7, 2745–2752 (1987).

    Article  CAS  Google Scholar 

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Authors and Affiliations

  1. The Cell Biology Laboratory, Hanhyo Institutes of Technology, Daiya-dong, san-6, Sihung-shi, Kyongki-do, 429-010, Korea

    Jaekyung Shim, Heejeong Lee, Jihyun Park, Hanshin Kim & Eui-Ju Choi

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  1. Jaekyung Shim
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  2. Heejeong Lee
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  3. Jihyun Park
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  4. Hanshin Kim
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  5. Eui-Ju Choi
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Correspondence to Eui-Ju Choi.

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Shim, J., Lee, H., Park, J. et al. A non-enzymatic p21 protein inhibitor of stress-activated protein kinases. Nature 381, 804–807 (1996). https://doi.org/10.1038/381804a0

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