Abstract
The candidate tumour-suppressor gene ING1 has been identified by using the genetic suppressor element (GSE) methodology1. ING1 encodes a nuclear protein, p33ING1, overexpression of which inhibits growth of different cell lines. The properties of p33ING1suggest 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 p33ING1and p53 proteins has been detected by immunoprecipitation. These results indicate that p33ING1is 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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Garkavtsev, I., Grigorian, I., Ossovskaya, V. et al. The candidate tumour suppressor p33ING1cooperates with p53 in cell growth control. Nature 391, 295–298 (1998). https://doi.org/10.1038/34675
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DOI: https://doi.org/10.1038/34675
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