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The Pleiotropy of Telomerase against Cell Death  

Sung, Young Hoon (Department of Molecular Cell Biology, Samsung Biomedical Research Institute, SungKyunkwan University School of Medicine)
Choi, Yoon Sik (Department of Molecular Cell Biology, Samsung Biomedical Research Institute, SungKyunkwan University School of Medicine)
Cheong, Cheolho (Department of Molecular Cell Biology, Samsung Biomedical Research Institute, SungKyunkwan University School of Medicine)
Lee, Han-Woong (Department of Molecular Cell Biology, Samsung Biomedical Research Institute, SungKyunkwan University School of Medicine)
Publication Information
Molecules and Cells / v.19, no.3, 2005 , pp. 303-309 More about this Journal
Abstract
The end of eukaryotic genomic DNA is capped by a specialized structure called as "telomere" which consists of the repetitive array of nucleotide sequence, TTAGGG, in humans and mice, and a variety of binding proteins. Telomerase is a ribonucleoprotein (RNP) complex responsible for the elongation of telomeres to maintain the genomic integrity, and is composed of telomerase reverse transcriptase (TERT), telomerase RNA component (TERC), and their associated factors regulating the catalytic activity of telomerase. Although it is now apparent that telomerase protects cells from apoptosis via the maintenance of genomic integrity by stabilizing telomeres, our understanding for the physiological role of telomerase is yet far from completion, and emerging evidence suggests that telomerase has additional extratelomeric roles in mediating cell survival and anti-apoptotic functions against various cytotoxic stresses. Here we summarize and discuss how telomerase and telomeres are involved in mediating cellular protection against apoptosis.
Keywords
Anti-apoptotic; Apoptosis; Cell Death; Extrate-lomeric; Survival; Telomerase; Telomere; TERT; TERC;
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Times Cited By KSCI : 1  (Citation Analysis)
Times Cited By Web Of Science : 25  (Related Records In Web of Science)
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1 Dudognon, C., Pendino, F., Hillion, J., Saumet, A., Lanotte, M., et al. (2004) Death receptor signaling regulatory function for telomerase: hTERT abolishes TRAIL-induced apoptosis, independently of telomere maintenance. Oncogene 23, 7469- 7474   DOI   ScienceOn
2 Etheridge, K. T., Banik, S. S., Armbruster, B. N., Zhu, Y., Terns, R. M., et al. (2002) The nucleolar localization domain of the catalytic subunit of human telomerase. J. Biol. Chem. 277, 24764-24770   DOI   ScienceOn
3 Fu, W., Killen, M., Culmsee, C., Dhar, S., Pandita, T. K., et al. (2000) The catalytic subunit of telomerase is expressed in developing brain neurons and serves a cell survivalpromoting function. J. Mol. Neurosci. 14, 3-15   DOI   ScienceOn
4 Li, S., Crothers, J., Haqq, C. M., and Blackburn, E. H. (2005) Cellular and gene expression responses involved in the rapid growth inhibition of human cancer cells by RNA interference- mediated depletion of telomerase RNA. J. Biol. Chem. [Epub ahead of print]
5 Saretzki, G., Ludwig, A., von Zglinicki, T., and Runnebaum, I. B. (2001) Ribozyme-mediated telomerase inhibition induces immediate cell loss but not telomere shortening in ovarian cancer cells. Cancer Gene Ther. 8, 827-834   DOI   ScienceOn
6 Smith, L. L., Coller, H. A., and Roberts, J. M. (2003) Telomerase modulates expression of growth-controlling genes and enhances cell proliferation. Nat. Cell Biol. 5, 474-479   DOI   ScienceOn
7 Wang, S. and El-Deiry W. S. (2003) TRAIL and apoptosis induction by TNF-family death receptors. Oncogene 22, 8628-8633   DOI   ScienceOn
8 Akiyama, M., Hideshima, T., Hayashi, T., Tai, Y. T., Mitsiades, C. S., et al. (2003) Nuclear factor-${\kappa}B$ p65 mediates tumor necrosis factor ${\alpha}$-induced nuclear translocation of telomerase reverse transcriptase protein. Cancer Res. 63, 18-21
9 Chan, S. W. and Blackburn, E. H. (2002) New ways not to make ends meet: telomerase, DNA damage proteins and heterochromatin. Oncogene 21, 553-563   DOI   ScienceOn
10 Martinou, J. C., Dubois-Dauphin, M., Staple, J. K., Rodriguez, I., Frankowski, H., et al. (1994) Overexpression of BCL-2 in transgenic mice protects neurons from naturally occurring cell death and experimental ischemia. Neuron 13, 1017–1030   DOI   ScienceOn
11 Caporaso, G. L., Lim, D. A., Alvarez-Buylla, A., and Chao, M. V. (2003) Telomerase activity in the subventricular zone of adult mice. Mol. Cell. Neurosci. 23, 693-702   DOI   ScienceOn
12 Zhu, H., Fu, W., and Mattson, M. P. (2000) The catalytic subunit of telomerase protects neurons against amyloid betapeptide- induced apoptosis. J. Neurochem. 75, 117-124   DOI
13 Wong, K. K., Chang, S., Weiler, S. R., Ganesan, S., Chaudhuri, J., et al. (2000) Telomere dysfunction impairs DNA repair and enhances sensitivity to ionizing radiation. Nat. Genet. 26, 85-88   DOI   ScienceOn
14 Blasco, M. A. (2003) Telomeres and cancer: a tale with many endings. Curr. Opin. Genet. Dev. 13, 70-76   DOI   ScienceOn
15 Kyo, S., Masutomi, K., Maida, Y., Kanaya, T., Yatabe, N., et al. (2003) Significance of immunological detection of human telomerase reverse transcriptase: re-evaluation of expression and localization of human telomerase reverse transcriptase. Am. J. Pathol. 163, 859-867   DOI   ScienceOn
16 Ren, J. G., Xia, H. L., Tian, Y. M., Just, T., Cai, G. P., et al. (2001b) Expression of telomerase inhibits hydroxyl radicalinduced apoptosis in normal telomerase negative human lung fibroblasts. FEBS Lett. 488, 133-138   DOI   ScienceOn
17 Seimiya, H., Sawada, H., Muramatsu, Y., Shimizu, M., Ohko, K., et al. (2000) Involvement of 14-3-3 proteins in nuclear localization of telomerase. EMBO J. 19, 2652-2661   DOI   ScienceOn
18 Blackburn, E. H. (1991) Structure and function of telomeres. Nature 350, 569-573   DOI   ScienceOn
19 Blackburn, E. H. (2001) Switching and signaling at the telomere. Cell 106, 661-673   DOI   ScienceOn
20 Masutomi, K., Yu, E. Y., Khurts, S., Ben-Porath, I., Currier, J. L., et al. (2003) Telomerase maintains telomere structure in normal human cells. Cell 114, 241-253   DOI   ScienceOn
21 Murphy, A. N., Bredesen, D. E., Cortopassi, G., Wang, E., and Fiskum, G. (1996) Bcl-2 potentiates the maximal calcium uptake capacity of neural cell mitochondria. Proc. Natl. Acad. Sci. USA 93, 9893-9898
22 Pendino, F., Flexor, M., Delhommeau, F., Buet, D., Lanotte, M., et al. (2001) Retinoids down-regulate telomerase and telomere length in a pathway distinct from leukemia cell differentiation. Proc. Natl. Acad. Sci. USA 98, 6662-6667
23 Bachand, F., Boisvert, F. M., Cote, J., Richard, S., and Autexier, C. (2002) The product of the survival of motor neuron (SMN) gene is a human telomerase-associated protein. Mol. Biol. Cell 13, 3192-3202   DOI   ScienceOn
24 Choi, D. W. (1985) Glutamate neurotoxicity in cortical cell culture is calcium dependent. Neurosci. Lett. 58, 293-297   DOI   ScienceOn
25 Chang, J. Y. (2004) Telomerase: a potential molecular marker and therapeutic target for cancer. Surg. Oncol. 87, 1-3   DOI   ScienceOn
26 Kang, H. J., Choi, Y. S., Hong, S. B., Kim, K. W., Woo, R. S., et al. (2004) Ectopic expression of the catalytic subunit of telomerase protects against brain injury resulting from ischemia and NMDA-induced neurotoxicity. J. Neurosci. 24, 1280-1287   DOI   ScienceOn
27 Li, S., Rosenberg, J. E., Donjacour, A. A., Botchkina, I. L., Hom, Y. K., et al. (2004) Rapid inhibition of cancer cell growth induced by lentiviral delivery and expression of mutant- template telomerase RNA and anti-telomerase shortinterfering RNA. Cancer Res. 64, 4833-4840   DOI   ScienceOn
28 Xu, D., Wang, Q., Gruber, A., Bjorkholm, M., Chen, Z., et al. (2000) Downregulation of telomerase reverse transcriptase mRNA expression by wild type p53 in human tumor cells. Oncogene 19, 5123-5133   DOI
29 Rahman, R., Latonen, L., and Wiman, K. G. (2005) hTERT antagonizes p53-induced apoptosis independently of telomerase activity. Oncogene 24, 1320-1327   DOI   ScienceOn
30 Kim, M. M., Rivera, M. A., Botchkina, I. L., Shalaby, R., Thor, A. D., et al. (2001) A low threshold level of expression of mutant-template telomerase RNA inhibits human tumor cell proliferation. Proc. Natl. Acad. Sci. USA 98, 7982-7987
31 Prowse, K. R. and Greider, C. W. (1995) Developmental and tissue-specific regulation of mouse telomerase and telomere length. Proc. Natl. Acad. Sci. USA 92, 4818-4822
32 Rizzuto, R., Pinton, P., Ferrari, D., Chami, M., Szabadkai, G., et al. (2003) Calcium and apoptosis: facts and hypotheses. Oncogene 22, 8619-8627   DOI   ScienceOn
33 Lee, H. W., Blasco, M. A., Gottlieb, G. J., Horner, J. W. 2nd, Greider, C. W., et al. (1998) Essential role of mouse telomerase in highly proliferative organs. Nature 392, 569-574   DOI   ScienceOn
34 Fu, W., Lu, C., and Mattson, M. P. (2002) Telomerase mediates the cell survival-promoting actions of brain-derived neurotrophic factor and secreted amyloid precursor protein in developing hippocampal neurons. J. Neurosci. 22, 10710-10719
35 Haendeler, J., Hoffmann, J., Brandes, R. P., Zeiher, A. M., and Dimmeler, S. (2003) Hydrogen peroxide triggers nuclear export of telomerase reverse transcriptase via Src kinase family- dependent phosphorylation of tyrosine 707. Mol. Cell Biol. 23, 4598-4610   DOI
36 Chin, L., Artandi, S. E., Shen, Q., Tam, A., Lee, S. L., et al. (1999) p53 deficiency rescues the adverse effects of telomere loss and cooperates with telomere dysfunction to accelerate carcinogenesis. Cell 97, 527-538   DOI   ScienceOn
37 Herbert, B. S., Pitts, A. E., Baker, S. I., Hamilton, S. E., Wright, W. E., et al. (1999) Inhibition of human telomerase in immortal human cells leads to progressive telomere shortening and cell death. Proc. Natl. Acad. Sci. USA 96, 14276-14281
38 Khurts, S., Masutomi, K., Delgermaa, L., Arai, K., Oishi, N., et al. (2004) Nucleolin interacts with telomerase. J. Biol. Chem. 279, 51508   DOI   ScienceOn
39 Chung, H. K., Cheong, C., Song, J., and Lee, H. W. (2005) Extratelomeric functions of telomerase. Curr. Mol. Med. 5, 233-241   DOI   ScienceOn
40 Chan, S. L., Tammariello, S. P., Estus, S., and Mattson, M. P. (1999) Prostate apoptosis response-4 mediates trophic factor withdrawal-induced apoptosis of hippocampal neurons: actions prior to mitochondrial dysfunction and caspase activation. J. Neurochem. 73, 502-512   DOI   ScienceOn
41 Cheong, C., Hong, K. U., and Lee, H. W. (2003) Mouse models for telomere and telomerase biology. Exp. Mol. Med. 35, 141-153   DOI   ScienceOn
42 von Zglinicki, T., Pilger, R., and Sitte, N. (2000) Accumulation of single-strand breaks is the major cause of telomere shortening in human fibroblasts. Free Radic. Biol. Med. 28, 64-74   DOI   ScienceOn
43 Blasco, M. A. and Hahn, W. C. (2003) Evolving views of telomerase and cancer. Trends Cell Biol. 13, 289-294   DOI   ScienceOn
44 Zhang, P., Chan, S. L., Fu, W., Mendoza, M., and Mattson, M. P. (2003) TERT suppresses apoptotis at a premitochondrial step by a mechanism requiring reverse transcriptase activity and 14-3-3 protein-binding ability. FASEB J. 17, 767-769
45 Kondo, S., Tanaka, Y., Kondo, Y., Hitomi, M., Barnett, G. H., et al. (1998) Antisense telomerase treatment: induction of two distinct pathways, apoptosis and differentiation. FASEB J. 12, 801-811
46 Ren, J. G., Xia, H. L., Just, T., and Dai, Y. R. (2001a) Hydroxyl radical-induced apoptosis in human tumor cells is associated with telomere shortening but not telomerase inhibition and caspase activation. FEBS Lett. 488, 123-132   DOI   ScienceOn
47 Wong, J. M., Kusdra, L., and Collins, K. (2002) Subnuclear shuttling of human telomerase induced by transformation and DNA damage. Nat. Cell Biol. 4, 731-736   DOI   ScienceOn
48 Cao, Y., Li, H., Deb, S., and Liu, J. P. (2002) TERT regulates cell survival independent of telomerase enzymatic activity. Oncogene 21, 3130-3138   DOI
49 Martin-Rivera, L., Herrera, E., Albar, J. P., and Blasco, M. A. (1998) Expression of mouse telomerase catalytic subunit in embryos and adult tissues. Proc. Natl. Acad. Sci. USA 95, 10471-10476
50 Akiyama, M., Yamada, O., Hideshima, T., Yanagisawa, T., Yokoi, K., et al. (2004) $TNF{\alpha}$ induces rapid activation and nuclear translocation of telomerase in human lymphocytes. Biochem. Biophys. Res. Commun. 316, 528-532   DOI   ScienceOn
51 Feng, J., Funk, W. D., Wang, S. S., Weinrich, S. L., Avilion, A. A., et al. (1995) The RNA component of human telomerase. Science 269, 1236–1241   DOI   ScienceOn
52 Yan, P., Benhattar, J., Seelentag, W., Stehle, J. C., and Bosman, F. T. (2004) Immunohistochemical localization of hTERT protein in human tissues. Histochem. Cell Biol. 121, 391-397   DOI