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TERT promotes cellular and organismal survival independently of telomerase activity

Oncogene volume 27, pages 3754–3760 (2008)Cite this article

Abstract

The expression level of the telomerase catalytic subunit (telomerase reverse transcriptase, TERT) positively correlates with cell survival after exposure to several lethal stresses. However, whether the protective role of TERT is independent of telomerase activity has not yet been clearly explored. Here, we genetically evaluated the protective roles of both TERT and telomerase activity against cell death induced by staurosporine (STS) and N-methyl-D-aspartic acid (NMDA). First generation (G1) TERT-deficient mouse embryonic fibroblasts (MEFs) displayed an increased sensitivity to STS, while TERT transgenic MEFs were more resistant to STS-induced apoptosis than wild-type. Deletion of the telomerase RNA component (TERC) failed to alter the sensitivity of TERT transgenic MEFs to STS treatment. Similarly, NMDA-induced excitotoxic cell death of primary neurons was suppressed by TERT, but not by TERC both in vitro and in vivo. Specifically, NMDA accelerated death of TERT-deficient mice, while TERT transgenic mice showed enhanced survival when compared with wild-type littermates after administration of NMDA. In addition, the transgenic expression of TERT protected motor neurons from apoptosis induced by sciatic nerve axotomy. These results indicate that telomerase activity is not essential for the protective function of TERT. This telomerase activity-independent TERT function may contribute to cancer development and aging independently of telomere lengthening.

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Acknowledgements

This work was supported by 21C Frontier Projects (Functional Human Genome Project, M106KB010014-07K0201-01410 and Brain Research Center, M103KV010025-07K2201-02510) from the MOST, SRC grant (MTRC, R11-2000-080-11004-0) from KOSEF, MOEHRD and the US National Institute for Aging (R01 AG23145, WCH). YHS is supported by BK21 of Yonsei University from MOEHRD.

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Author notes

  1. C Cheong

    Present address: 9Current address: Laboratory of Cellular Physiology and Immunology and Chris Browne Center for Immunology and Immune Diseases, The Rockefeller University, 1230 York Avenue, New York, NY 10065, USA.,

  2. J Lee, Y H Sung and C Cheong: These authors contributed equally to this work.

Authors and Affiliations

  1. Department of Molecular Cell Biology, Sungkyunkwan University School of Medicine, Suwon, Republic of Korea

    J Lee & C Cheong

  2. Department of Biochemistry, Brain Korea 21 Program, Yonsei University, Seoul, Republic of Korea

    Y H Sung, Y S Choi, H K Jeon & H-W Lee

  3. Department of Anatomy, College of Medicine, Brain Korea 21 Program, Korea University, Seoul, Republic of Korea

    W Sun

  4. Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, USA

    W C Hahn

  5. Department of Medicine, Brigham and Women's Hospital, Boston, MA, USA

    W C Hahn

  6. Department of Medicine, Harvard Medical School, Boston, MA, USA

    W C Hahn

  7. Department of Gene Mechanisms, Kyoto University, Kyoto, Japan

    F Ishikawa

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Supplementary Information accompanies the paper on the Oncogene website (http://www.nature.com/onc).

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Lee, J., Sung, Y., Cheong, C. et al. TERT promotes cellular and organismal survival independently of telomerase activity. Oncogene 27, 3754–3760 (2008). https://doi.org/10.1038/sj.onc.1211037

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