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Molecular interactions between telomerase and the tumor suppressor protein p53 in vitro

Oncogene volume 18, pages 6785–6794 (1999)Cite this article

Abstract

The telomere DNA polymerase (telomerase) and the tumor suppressor protein p53 are frequently associated with human cancers, and activation of telomerase and inactivation of p53 involved in cancer cell immortalization. In this report, we demonstrate a direct interaction of telomerase with p53 in the nuclear lysates of human breast cancer cells, and with recombinant human p53, by affinity chromatography and immunoprecipitation. On activity criteria, the interaction is between the carboxyl-terminal region of p53 and a region close to the amino-terminus of human telomerase-associated protein 1 (hTEP1). Incubation of recombinant p53 with nuclear telomerase extracts results in inhibition of telomerase activity, with the C-terminal region of p53 being essential for inhibition. This effect is not mediated by binding to telomerase substrate DNA, but requires the region near the N-terminus of hTEP1, in that a synthetic peptide derived from this region of hTEP1 similarly inhibits telomerase activity. Together, these in vitro interactions between telomerase and p53 suggest that the activity of telomerase may be regulated by p53, down-regulation of which in turn would favor up-regulation of telomerase activity in cancer cell development.

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Acknowledgements

We thank Drs Arnold J Levine and Bruce Stillman for kindly providing p53 cDNAs, Dr Roger Reddel for discussion and Ms Linlin Zhao for technical assistance. This work was supported by grants from the Australia Research Council and National Health and Medical Research Council of Australia.

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  1. Molecular Signaling Laboratory, Baker Medical Research Institute, Commercial Road, Prahran, Victoria, Australia

    He Li, Ying Cao, Michael C Berndt, John W Funder & Jun-Ping Liu

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Li, H., Cao, Y., Berndt, M. et al. Molecular interactions between telomerase and the tumor suppressor protein p53 in vitro. Oncogene 18, 6785–6794 (1999). https://doi.org/10.1038/sj.onc.1203061

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