The candidate tumour suppressor p33ING1cooperates with p53 in cell growth control (original) (raw)

Nature volume 391, pages 295–298 (1998)Cite this article

Abstract

The candidate tumour-suppressor gene ING1 has been identified by using the genetic suppressor element (GSE) methodology1. ING1 encodes a nuclear protein, p33_ING1_, overexpression of which inhibits growth of different cell lines. The properties of p33_ING1_suggest its involvement in the negative regulation of cell proliferation and in the control of cellular ageing, anchorage dependence and apoptosis1,2,3. These cellular functions depend largely on the activity of p53, a tumour-suppressor gene that determines the cellular response to various types of stress4. Here we report that the biological effects of ING1 and p53 are interrelated and require the activity of both genes: neither of the two genes can, on its own, cause growth inhibition when the other one is suppressed. Furthermore, activation of transcription from the p21/WAF1 promoter, a key mechanism of p53-mediated growth control, depends on the expression of ING1. A physical association between p33_ING1_and p53 proteins has been detected by immunoprecipitation. These results indicate that p33_ING1_is a component of the p53 signalling pathway that cooperates with p53 in the negative regulation of cell proliferation by modulating p53-dependent transcriptional activation.

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Acknowledgements

We thank R. Davidson and E. Feinstein for reading the manuscript, and C. Zelnick for help with manuscript preparation. This work was supported by NIH grants to A.V.G., by a Fogarty International Collaboration Award to A.V.G. and P.M.C., and fellowships from NCI to I.A.G. and V.S.O.

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Author notes

  1. Valeria S. Ossovskaya
    Present address: Department of Pathology, University of California, San Francisco, 94143, California, USA
  2. Igor Garkavtsev
    Present address: Department of Functional Genomics, Genome Therapeutics Corporation, Waltham, Massachusetts, 02154, USA
  3. Igor Garkavtsev and Irina A. Grigorian: These authors contributed equally to this work.

Authors and Affiliations

  1. Department of Medical Biochemistry and Southern Alberta Cancer Research Center, University of Calgary, Calgary, T2N 4N1, Alberta, Canada
    Igor Garkavtsev
  2. Department of Molecular Genetics, College of Medicine, University of Illinois at Chicago, Chicago, 60607, Illinois, USA
    Irina A. Grigorian & Andrei V. Gudkov
  3. Engelhardt Institute of Molecular Biology, Moscow, Russia
    Valeria S. Ossovskaya & Peter M. Chumakov
  4. Cleveland Clinic Foundation, Cleveland, 44195, Ohio, USA
    Mikhail V. Chernov

Authors

  1. Igor Garkavtsev
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  2. Irina A. Grigorian
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  3. Valeria S. Ossovskaya
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  4. Mikhail V. Chernov
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  5. Peter M. Chumakov
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  6. Andrei V. Gudkov
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Corresponding author

Correspondence toAndrei V. Gudkov.

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Garkavtsev, I., Grigorian, I., Ossovskaya, V. et al. The candidate tumour suppressor p33_ING1_cooperates with p53 in cell growth control.Nature 391, 295–298 (1998). https://doi.org/10.1038/34675

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