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TERT regulates cell survival independent of telomerase enzymatic activity

Oncogene volume 21, pages 3130–3138 (2002)Cite this article

Abstract

Human telomerase reverse transcriptase (hTERT), the catalytic subunit of telomerase, plays a pivotal role in the maintenance of telomeres and cell proliferation. Here we report that down-regulation of hTERT induces apoptosis independently of telomerase enzymatic activity in human breast cancer cells. Expression of a hTERT mutant lacking telomerase activity rescues the cells with lowered telomerase without inducing cell death. With similar patterns of subcellular distribution to that of the tumor suppressor protein p53 during mitosis, hTERT interacts with p53 and poly(ADP-ribose) polymerase (PARP). Decreasing p53 expression in intact cells worsens, and increasing p53 prevents, cell death induced by lowering hTERT. Thus, hTERT maintains cell survival and proliferation via both telomerase enzymatic activity-dependent telomere lengthening and enzymatic activity-independent intermolecular interactions involving p53 and PARP.

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Abbreviations

TERT:

telomerase reverse transcriptase

PARP:

poly(ADP-ribose) polymerase

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Acknowledgements

We would like to thank Andrzej Kilian and Roger Reddel for hTERT cDNA and Bruce Stillman for p53 expression plasmids. This work was supported by grants from the Australia Research Council, National Health and Medical Research Council of Australia and Anti-Cancer Council of Victoria. Y Cao was a recipient of postgraduate research scholarship from Anticancer Council of Victoria.

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Authors and Affiliations

  1. Molecular Signaling Laboratory, Baker Medical Research Institute, Commercial Road, Prahran, 3181, Victoria, Australia

    Ying Cao, He Li, Siddhartha Deb & Jun-Ping Liu

  2. Department of Pathology and Immunology, Monash University Medical School, Commercial Road, Prahran, 3181, Victoria, Australia

    Jun-Ping Liu

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  1. Ying Cao
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  2. He Li
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Correspondence to Jun-Ping Liu.

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Cao, Y., Li, H., Deb, S. et al. TERT regulates cell survival independent of telomerase enzymatic activity. Oncogene 21, 3130–3138 (2002). https://doi.org/10.1038/sj.onc.1205419

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