TERT promotes cellular and organismal survival independently of telomerase activity

J. Lee, Y. H. Sung, C. Cheong, Y. S. Choi, H. K. Jeon, Woong Sun, W. C. Hahn, F. Ishikawa, H. W. Lee

Research output: Contribution to journalArticle

103 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)3754-3760
Number of pages7
JournalOncogene
Volume27
Issue number26
DOIs
Publication statusPublished - 2008 Jun 12

Fingerprint

Telomerase
Staurosporine
N-Methylaspartate
Transgenic Mice
Fibroblasts
Cell Death
Telomere Homeostasis
Apoptosis
Axotomy
Motor Neurons
Sciatic Nerve

Keywords

  • Cell death
  • Cellular protection
  • Telomerase
  • Telomerase activity
  • TERT

ASJC Scopus subject areas

  • Molecular Biology
  • Cancer Research
  • Genetics

Cite this

Lee, J., Sung, Y. H., Cheong, C., Choi, Y. S., Jeon, H. K., Sun, W., ... Lee, H. W. (2008). TERT promotes cellular and organismal survival independently of telomerase activity. Oncogene, 27(26), 3754-3760. https://doi.org/10.1038/sj.onc.1211037

TERT promotes cellular and organismal survival independently of telomerase activity. / Lee, J.; Sung, Y. H.; Cheong, C.; Choi, Y. S.; Jeon, H. K.; Sun, Woong; Hahn, W. C.; Ishikawa, F.; Lee, H. W.

In: Oncogene, Vol. 27, No. 26, 12.06.2008, p. 3754-3760.

Research output: Contribution to journalArticle

Lee, J, Sung, YH, Cheong, C, Choi, YS, Jeon, HK, Sun, W, Hahn, WC, Ishikawa, F & Lee, HW 2008, 'TERT promotes cellular and organismal survival independently of telomerase activity', Oncogene, vol. 27, no. 26, pp. 3754-3760. https://doi.org/10.1038/sj.onc.1211037
Lee, J. ; Sung, Y. H. ; Cheong, C. ; Choi, Y. S. ; Jeon, H. K. ; Sun, Woong ; Hahn, W. C. ; Ishikawa, F. ; Lee, H. W. / TERT promotes cellular and organismal survival independently of telomerase activity. In: Oncogene. 2008 ; Vol. 27, No. 26. pp. 3754-3760.
@article{b9cad9976e654ba0aaa118fb17972fbc,
title = "TERT promotes cellular and organismal survival independently of telomerase activity",
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.",
keywords = "Cell death, Cellular protection, Telomerase, Telomerase activity, TERT",
author = "J. Lee and Sung, {Y. H.} and C. Cheong and Choi, {Y. S.} and Jeon, {H. K.} and Woong Sun and Hahn, {W. C.} and F. Ishikawa and Lee, {H. W.}",
year = "2008",
month = "6",
day = "12",
doi = "10.1038/sj.onc.1211037",
language = "English",
volume = "27",
pages = "3754--3760",
journal = "Oncogene",
issn = "0950-9232",
publisher = "Nature Publishing Group",
number = "26",

}

TY - JOUR

T1 - TERT promotes cellular and organismal survival independently of telomerase activity

AU - Lee, J.

AU - Sung, Y. H.

AU - Cheong, C.

AU - Choi, Y. S.

AU - Jeon, H. K.

AU - Sun, Woong

AU - Hahn, W. C.

AU - Ishikawa, F.

AU - Lee, H. W.

PY - 2008/6/12

Y1 - 2008/6/12

N2 - 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.

AB - 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.

KW - Cell death

KW - Cellular protection

KW - Telomerase

KW - Telomerase activity

KW - TERT

UR - http://www.scopus.com/inward/record.url?scp=45949096290&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=45949096290&partnerID=8YFLogxK

U2 - 10.1038/sj.onc.1211037

DO - 10.1038/sj.onc.1211037

M3 - Article

VL - 27

SP - 3754

EP - 3760

JO - Oncogene

JF - Oncogene

SN - 0950-9232

IS - 26

ER -