Molecular regulation of telomerase activity in aging

Craig Nicholls1,3, He Li1, Jian-Qiu Wang2, Jun-Ping Liu1,2,3,4()

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Protein Cell ›› 2011, Vol. 2 ›› Issue (9) : 726-738. DOI: 10.1007/s13238-011-1093-3
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REVIEW

Molecular regulation of telomerase activity in aging

  • Craig Nicholls1,3, He Li1, Jian-Qiu Wang2, Jun-Ping Liu1,2,3,4()
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Abstract

The process of aging is mitigated by the maintenance and repair of chromosome ends (telomeres), resulting in extended lifespan. This review examines the molecular mechanisms underlying the actions and regulation of the enzyme telomerase reverse transcriptase (TERT), which functions as the primary mechanism of telomere maintenance and regulates cellular life expectancy. Underpinning increased cell proliferation, telomerase is also a key factor in facilitating cancer cell immortalization. The review focuses on aspects of hormonal regulations of telomerase, and the intracellular pathways that converge to regulate telomerase activity with an emphasis on molecular interactions at protein and gene levels. In addition, the basic structure and function of two key telomerase enzyme components—the catalytic subunit TERT and the template RNA (TERC) are discussed briefly.

Keywords

telomerase / aging / telomerase reverse transcriptase (TERT)

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Craig Nicholls, He Li, Jian-Qiu Wang, Jun-Ping Liu. Molecular regulation of telomerase activity in aging. Prot Cell, 2011, 2(9): 726‒738 https://doi.org/10.1007/s13238-011-1093-3

References

[1] Akalin, A., Elmore, L.W., Forsythe, H.L., Amaker, B.A., McCollum, E.D., Nelson, P.S., Ware, J.L., and Holt, S.E. (2001). A novel mechanism for chaperone-mediated telomerase regulation during prostate cancer progression. Cancer Res 61, 4791–4796 11406554.
[2] Allsopp, R.C., Vaziri, H., Patterson, C., Goldstein, S., Younglai, E.V., Futcher, A.B., Greider, C.W., and Harley, C.B. (1992). Telomere length predicts replicative capacity of human fibroblasts. Proc Natl Acad Sci U S A 89, 10114–10118 1438199.
[3] Armanios, M. (2009). Syndromes of Telomere Shortening. Annu Rev Genomics Hum Genet 10, 45–61 .
[4] Armbruster, B.N., Banik, S.S., Guo, C., Smith, A.C., and Counter, C.M. (2001). N-terminal domains of the human telomerase catalytic subunit required for enzyme activity in vivo. Mol Cell Biol 21, 7775–7786 11604512.
[5] Atzmon, G., Cho, M., Cawthon, R.M., Budagov, T., Katz, M., Yang, X., Siegel, G., Bergman, A., Huffman, D.M., Schechter, C.B., (2010). Evolution in health and medicine Sackler colloquium: Genetic variation in human telomerase is associated with telomere length in Ashkenazi centenarians. Proc Natl Acad Sci U S A 107, 1710–1717 19915151.
[6] Autexier, C., Pruzan, R., Funk, W.D., and Greider, C.W. (1996). Reconstitution of human telomerase activity and identification of a minimal functional region of the human telomerase RNA. EMBO J 15, 5928–5935 8918470.
[7] Ayouaz, A., Raynaud, C., Heride, C., Revaud, D., and Sabatier, L. (2008). Telomeres: hallmarks of radiosensitivity. Biochimie 90, 60–72 18006207.
[8] Bachand, F., and Autexier, C. (2001). Functional regions of human telomerase reverse transcriptase and human telomerase RNA required for telomerase activity and RNA-protein interactions. Mol Cell Biol 21, 1888–1897 11238925.
[9] Bagheri, S., Nosrati, M., Li, S., Fong, S., Torabian, S., Rangel, J., Moore, D.H., Federman, S., Laposa, R.R., Baehner, F.L., (2006). Genes and pathways downstream of telomerase in melanoma metastasis. Proc Natl Acad Sci U S A 103, 11306–11311 16847266.
[10] Banik, S.S., Guo, C., Smith, A.C., Margolis, S.S., Richardson, D.A., Tirado, C.A., and Counter, C.M. (2002). C-terminal regions of the human telomerase catalytic subunit essential for in vivo enzyme activity. Mol Cell Biol 22, 6234–6246 12167716.
[11] Banks, W.A., Morley, J.E., Farr, S.A., Price, T.O., Ercal, N., Vidaurre, I., and Schally, A.V. (2010). Effects of a growth hormone-releasing hormone antagonist on telomerase activity, oxidative stress, longevity, and aging in mice. Proc Natl Acad Sci U S A 107, 22272–22277 21135231.
[12] Bayne, S., Jones, M.E., Li, H., Pinto, A.R., Simpson, E.R., and Liu, J.P. (2008). Estrogen deficiency leads to telomerase inhibition, telomere shortening and reduced cell proliferation in the adrenal gland of mice. Cell Res 18, 1141–1150 18936784.
[13] Bayne, S., Li, H., Jones, M.E., Pinto, A.R., van Sinderen, M., Drummond, A., Simpson, E.R., and Liu, J.P. (2011). Estrogen deficiency reversibly induces telomere shortening in mouse granulosa cells and ovarian aging in vivo. Protein Cell 2, 333–346 21574023.
[14] Britt, K.L., Drummond, A.E., Dyson, M., Wreford, N.G., Jones, M.E., Simpson, E.R., and Findlay, J.K. (2001). The ovarian phenotype of the aromatase knockout (ArKO) mouse. J Steroid Biochem Mol Biol 79, 181–185 11850223.
[15] Britt, K.L., Kerr, J., O’Donnell, L., Jones, M.E., Drummond, A.E., Davis, S.R., Simpson, E.R., and Findlay, J.K. (2002). Estrogen regulates development of the somatic cell phenotype in the eutherian ovary. FASEB J 16, 1389–1397 12205030.
[16] Browner, W.S., Kahn, A.J., Ziv, E., Reiner, A.P., Oshima, J., Cawthon, R.M., Hsueh, W.C., and Cummings, S.R. (2004). The genetics of human longevity. Am J Med 117, 851–860 15589490.
[17] Bryan, T.M., Goodrich, K.J., and Cech, T.R. (2000). Telomerase RNA bound by protein motifs specific to telomerase reverse transcriptase. Mol Cell 6, 493–499 10983995.
[18] Calado, R.T., and Young, N.S. (2009). Telomere diseases. N Engl J Med 361, 2353–2365 20007561.
[19] Cassar, L., Li, H., Pinto, A.R., Nicholls, C., Bayne, S., and Liu, J.P. (2008). Bone morphogenetic protein-7 inhibits telomerase activity, telomere maintenance, and cervical tumor growth. Cancer Res 68, 9157–9166 19010887.
[20] Cha, Y., Kwon, S.J., Seol, W., and Park, K.S. (2008). Estrogen receptor-alpha mediates the effects of estradiol on telomerase activity in human mesenchymal stem cells. Mol Cells 26, 454–458 18719354.
[21] Chai, W., Ford, L.P., Lenertz, L., Wright, W.E., and Shay, J.W. (2002). Human Ku70/80 associates physically with telomerase through interaction with hTERT. J Biol Chem 277, 47242–47247 12377759.
[22] Chang, J.T., Lu, Y.C., Chen, Y.J., Tseng, C.P., Chen, Y.L., Fang, C.W., and Cheng, A.J. (2006). hTERT phosphorylation by PKC is essential for telomerase holoprotein integrity and enzyme activity in head neck cancer cells. Br J Cancer 94, 870–878 16508638.
[23] Chen, J.L., Blasco, M.A., and Greider, C.W. (2000). Secondary structure of vertebrate telomerase RNA. Cell 100, 503–514 10721988.
[24] Cohen, S.B., Graham, M.E., Lovrecz, G.O., Bache, N., Robinson, P.J., and Reddel, R.R. (2007). Protein composition of catalytically active human telomerase from immortal cells. Science 315, 1850–1853 17395830.
[25] Colgin, L.M., Wilkinson, C., Englezou, A., Kilian, A., Robinson, M.O., and Reddel, R.R. (2000). The hTERTalpha splice variant is a dominant negative inhibitor of telomerase activity. Neoplasia 2, 426–432 11191109.
[26] Collins, K. (2006). The biogenesis and regulation of telomerase holoenzymes. Nat Rev Mol Cell Biol 7, 484–494 16829980.
[27] Cong, Y.S., Wen, J., and Bacchetti, S. (1999). The human telomerase catalytic subunit hTERT: organization of the gene and characterization of the promoter. Hum Mol Genet 8, 137–142 9887342.
[28] Counter, C.M., Meyerson, M., Eaton, E.N., Ellisen, L.W., Caddle, S.D., Haber, D.A., and Weinberg, R.A. (1998). Telomerase activity is restored in human cells by ectopic expression of hTERT (hEST2), the catalytic subunit of telomerase. Oncogene 16, 1217–1222 9528864.
[29] Cuthbert, A.P., Bond, J., Trott, D.A., Gill, S., Broni, J., Marriott, A., Khoudoli, G., Parkinson, E.K., Cooper, C.S., and Newbold, R.F. (1999). Telomerase repressor sequences on chromosome 3 and induction of permanent growth arrest in human breast cancer cells. J Natl Cancer Inst 91, 37–45 9890168.
[30] Dallaire, F., Dupuis, S., Fiset, S., and Chabot, B. (2000). Heterogeneous nuclear ribonucleoprotein A1 and UP1 protect mammalian telomeric repeats and modulate telomere replication in vitro. J Biol Chem 275, 14509–14516 10799534.
[31] Dang, C.V. (1999). c-Myc target genes involved in cell growth, apoptosis, and metabolism. Mol Cell Biol 19, 1–11 9858526.
[32] de Lange, T. (2009). How telomeres solve the end-protection problem. Science 326, 948–952 19965504.
[33] Denchi, E.L. (2009). Give me a break: how telomeres suppress the DNA damage response. DNA Repair (Amst) 8, 1118–1126 19482563.
[34] Dessain, S.K., Yu, H., Reddel, R.R., Beijersbergen, R.L., and Weinberg, R.A. (2000). Methylation of the human telomerase gene CpG island. Cancer Res 60, 537–541 10676632.
[35] Devereux, T.R., Horikawa, I., Anna, C.H., Annab, L.A., Afshari, C.A., and Barrett, J.C. (1999). DNA methylation analysis of the promoter region of the human telomerase reverse transcriptase (hTERT) gene. Cancer Res 59, 6087–6090 10626795.
[36] Feng, J., Funk, W.D., Wang, S.S., Weinrich, S.L., Avilion, A.A., Chiu, C.P., Adams, R.R., Chang, E., Allsopp, R.C., Yu, J., (1995). The RNA component of human telomerase. Science 269, 1236–1241 7544491.
[37] Fiset, S., and Chabot, B. (2001). hnRNP A1 may interact simultaneously with telomeric DNA and the human telomerase RNA in vitro. Nucleic Acids Res 29, 2268–2275 11376145.
[38] Fisher, C.R., Graves, K.H., Parlow, A.F., and Simpson, E.R. (1998). Characterization of mice deficient in aromatase (ArKO) because of targeted disruption of the cyp19 gene. Proc Natl Acad Sci U S A 95, 6965–6970 9618522.
[39] Forsythe, H.L., Jarvis, J.L., Turner, J.W., Elmore, L.W., and Holt, S.E. (2001). Stable association of hsp90 and p23, but Not hsp70, with active human telomerase. J Biol Chem 276, 15571–15574 11274138.
[40] Friedman, K.L., and Cech, T.R. (1999). Essential functions of amino-terminal domains in the yeast telomerase catalytic subunit revealed by selection for viable mutants. Genes Dev 13, 2863–2874 10557213.
[41] Geserick, C., Tejera, A., González-Suárez, E., Klatt, P., and Blasco, M.A. (2006). Expression of mTert in primary murine cells links the growth-promoting effects of telomerase to transforming growth factor-beta signaling. Oncogene 25, 4310–4319 16501597.
[42] Gillis, A.J., Schuller, A.P., and Skordalakes, E. (2008). Structure of the Tribolium castaneum telomerase catalytic subunit TERT. Nature 455, 633–637 18758444.
[43] González-Suárez, E., Geserick, C., Flores, J.M., and Blasco, M.A. (2005). Antagonistic effects of telomerase on cancer and aging in K5-mTert transgenic mice. Oncogene 24, 2256–2270 15688016.
[44] González-Suárez, E., Samper, E., Ramírez, A., Flores, J.M., Martín-Caballero, J., Jorcano, J.L., and Blasco, M.A. (2001). Increased epidermal tumors and increased skin wound healing in transgenic mice overexpressing the catalytic subunit of telomerase, mTERT, in basal keratinocytes. EMBO J 20, 2619–2630 11387197.
[45] Grasselli, A., Nanni, S., Colussi, C., Aiello, A., Benvenuti, V., Ragone, G., Moretti, F., Sacchi, A., Bacchetti, S., Gaetano, C., (2008). Estrogen receptor-alpha and endothelial nitric oxide synthase nuclear complex regulates transcription of human telomerase. Circ Res 103, 34–42 18519947.
[46] Greenberg, R.A., O’Hagan, R.C., Deng, H., Xiao, Q., Hann, S.R., Adams, R.R., Lichtsteiner, S., Chin, L., Morin, G.B., and DePinho, R.A. (1999). Telomerase reverse transcriptase gene is a direct target of c-Myc but is not functionally equivalent in cellular transformation. Oncogene 18, 1219–1226 10022128.
[47] Greider, C.W., and Blackburn, E.H. (1985). Identification of a specific telomere terminal transferase activity in Tetrahymena extracts. Cell 43, 405–413 3907856.
[48] Greider, C.W., and Blackburn, E.H. (1987). The telomere terminal transferase of Tetrahymena is a ribonucleoprotein enzyme with two kinds of primer specificity. Cell 51, 887–898 3319189.
[49] Günes, C., Lichtsteiner, S., Vasserot, A.P., and Englert, C. (2000). Expression of the hTERT gene is regulated at the level of transcriptional initiation and repressed by Mad1. Cancer Res 60, 2116–2121 10786671.
[50] Guo, C., Armbruster, B.N., Price, D.T., and Counter, C.M. (2003). In vivo regulation of hTERT expression and telomerase activity by androgen. J Urol 170, 615–618 12853842.
[51] Hahn, W.C., Stewart, S.A., Brooks, M.W., York, S.G., Eaton, E., Kurachi, A., Beijersbergen, R.L., Knoll, J.H., Meyerson, M., and Weinberg, R.A. (1999). Inhibition of telomerase limits the growth of human cancer cells. Nat Med 5, 1164–1170 10502820.
[52] Harley, C.B. (1991). Telomere loss: mitotic clock or genetic time bomb? Mutat Res 256, 271–282 1722017.
[53] Harley, C.B. (2008). Telomerase and cancer therapeutics. Nat Rev Cancer 8, 167–179 18256617.
[54] Heiss, N.S., Knight, S.W., Vulliamy, T.J., Klauck, S.M., Wiemann, S., Mason, P.J., Poustka, A., and Dokal, I. (1998). X-linked dyskeratosis congenita is caused by mutations in a highly conserved gene with putative nucleolar functions. Nat Genet 19, 32–38 9590285.
[55] Herbert, B., Pitts, A.E., Baker, S.I., Hamilton, S.E., Wright, W.E., Shay, J.W., and Corey, D.R. (1999). Inhibition of human telomerase in immortal human cells leads to progressive telomere shortening and cell death. Proc Natl Acad Sci U S A 96, 14276–14281 10588696.
[56] Herrera, E., Samper, E., and Blasco, M.A. (1999). Telomere shortening in mTR-/- embryos is associated with failure to close the neural tube. EMBO J 18, 1172–1181 10064584.
[57] Holt, S.E., Aisner, D.L., Baur, J., Tesmer, V.M., Dy, M., Ouellette, M., Trager, J.B., Morin, G.B., Toft, D.O., Shay, J.W., (1999). Functional requirement of p23 and Hsp90 in telomerase complexes. Genes Dev 13, 817–826 10197982.
[58] Horikawa, I., Cable, P.L., Afshari, C., and Barrett, J.C. (1999). Cloning and characterization of the promoter region of human telomerase reverse transcriptase gene. Cancer Res 59, 826–830 10029071.
[59] Horikawa, I., Oshimura, M., and Barrett, J.C. (1998). Repression of the telomerase catalytic subunit by a gene on human chromosome 3 that induces cellular senescence. Mol Carcinog 22, 65–72 9655250.
[60] Huard, S., Moriarty, T.J., and Autexier, C. (2003). The C terminus of the human telomerase reverse transcriptase is a determinant of enzyme processivity. Nucleic Acids Res 31, 4059–4070 12853623.
[61] Jacobs, S.A., Podell, E.R., and Cech, T.R. (2006). Crystal structure of the essential N-terminal domain of telomerase reverse transcriptase. Nat Struct Mol Biol 13, 218–225 16462747.
[62] Jaskelioff, M., Muller, F.L., Paik, J.H., Thomas, E., Jiang, S., Adams, A.C., Sahin, E., Kost-Alimova, M., Protopopov, A., Cadi?anos, J., (2011). Telomerase reactivation reverses tissue degeneration in aged telomerase-deficient mice. Nature 469, 102–106 21113150.
[63] Kalantaridou, S.N., Naka, K.K., Bechlioulis, A., Makrigiannakis, A., Michalis, L., and Chrousos, G.P. (2006). Premature ovarian failure, endothelial dysfunction and estrogen-progestogen replacement. Trends Endocrinol Metab 17, 101–109 16515863.
[64] Kang, S.S., Kwon, T., Kwon, D.Y., and Do, S.I. (1999). Akt protein kinase enhances human telomerase activity through phosphorylation of telomerase reverse transcriptase subunit. J Biol Chem 274, 13085–13090 10224060.
[65] Kelleher, C., Teixeira, M.T., F?rstemann, K., and Lingner, J. (2002). Telomerase: biochemical considerations for enzyme and substrate. Trends Biochem Sci 27, 572–579 12417133.
[66] Kiaris, H., and Schally, A.V. (1999). Decrease in telomerase activity in U-87MG human glioblastomas after treatment with an antagonist of growth hormone-releasing hormone. Proc Natl Acad Sci U S A 96, 226–231 9874800.
[67] Kimura, A., Ohmichi, M., Kawagoe, J., Kyo, S., Mabuchi, S., Takahashi, T., Ohshima, C., Arimoto-Ishida, E., Nishio, Y., Inoue, M., (2004). Induction of hTERT expression and phosphorylation by estrogen via Akt cascade in human ovarian cancer cell lines. Oncogene 23, 4505–4515 15048073.
[68] Kimura, M., Barbieri, M., Gardner, J.P., Skurnick, J., Cao, X., van Riel, N., Rizzo, M.R., Paoliso, G., and Aviv, A. (2007). Leukocytes of exceptionally old persons display ultra-short telomeres. Am J Physiol Regul Integr Comp Physiol 293, R2210–R2217 17898116.
[69] Kimura, M., Cherkas, L.F., Kato, B.S., Demissie, S., Hjelmborg, J.B., Brimacombe, M., Cupples, A., Hunkin, J.L., Gardner, J.P., Lu, X., (2008). Offspring’s leukocyte telomere length, paternal age, and telomere elongation in sperm. PLoS Genet 4, e3718282113.
[70] Kugoh, H., Shigenami, K., Funaki, K., Barrett, J.C., and Oshimura, M. (2003). Human chromosome 5 carries a putative telomerase repressor gene. Genes Chromosomes Cancer 36, 37–47 12461748.
[71] Kyo, S., Takakura, M., Kanaya, T., Zhuo, W., Fujimoto, K., Nishio, Y., Orimo, A., and Inoue, M. (1999). Estrogen activates telomerase. Cancer Res 59, 5917–5921 10606235.
[72] Kyo, S., Takakura, M., Taira, T., Kanaya, T., Itoh, H., Yutsudo, M., Ariga, H., and Inoue, M. (2000). Sp1 cooperates with c-Myc to activate transcription of the human telomerase reverse transcriptase gene (hTERT). Nucleic Acids Res 28, 669–677 10637317.
[73] LaBranche, H., Dupuis, S., Ben-David, Y., Bani, M.R., Wellinger, R.J., and Chabot, B. (1998). Telomere elongation by hnRNP A1 and a derivative that interacts with telomeric repeats and telomerase. Nat Genet 19, 199–202 9620782.
[74] Lai, C.K., Mitchell, J.R., and Collins, K. (2001). RNA binding domain of telomerase reverse transcriptase. Mol Cell Biol 21, 990–1000 11158287.
[75] Laviolette, L.A., Garson, K., Macdonald, E.A., Senterman, M.K., Courville, K., Crane, C.A., and Vanderhyden, B.C. (2010). 17beta-estradiol accelerates tumor onset and decreases survival in a transgenic mouse model of ovarian cancer. Endocrinology 151, 929–938 20056833.
[76] Lee, H.W., Blasco, M.A., Gottlieb, G.J., Horner, J.W. 2nd, Greider, C.W., and DePinho, R.A. (1998). Essential role of mouse telomerase in highly proliferative organs. Nature 392, 569–574 9560153.
[77] Li, H., Pinto, A.R., Duan, W., Li, J., Toh, B.H., and Liu, J.P. (2005). Telomerase down-regulation does not mediate PC12 pheochromocytoma cell differentiation induced by NGF, but requires MAP kinase signalling. J Neurochem 95, 891–901 16248892.
[78] Li, H., Zhao, L., Yang, Z., Funder, J.W., and Liu, J.P. (1998). Telomerase is controlled by protein kinase Calpha in human breast cancer cells. J Biol Chem 273, 33436–33442 9837921.
[79] Lin, J., Kroenke, C.H., Epel, E., Kenna, H.A., Wolkowitz, O.M., Blackburn, E., and Rasgon, N.L. (2011). Greater endogenous estrogen exposure is associated with longer telomeres in postmenopausal women at risk for cognitive decline. Brain Res 1379, 224–231 20965155.
[80] Ling, S., Zhou, L., Li, H., Dai, A., Liu, J.P., Komesaroff, P.A., and Sudhir, K. (2006). Effects of 17beta-estradiol on growth and apoptosis in human vascular endothelial cells: influence of mechanical strain and tumor necrosis factor-alpha. Steroids 71, 799–808 16806337.
[81] Liu, J.P., Chen, S.M., Cong, Y.S., Nicholls, C., Zhou, S.F., Tao, Z.Z., and Li, H. (2010). Regulation of telomerase activity by apparently opposing elements. Ageing Res Rev 9, 245–256 20362078.
[82] Loayza, D., and De Lange, T. (2003). POT1 as a terminal transducer of TRF1 telomere length control. Nature 423, 1013–1018 12768206.
[83] Lopatina, N.G., Poole, J.C., Saldanha, S.N., Hansen, N.J., Key, J.S., Pita, M.A., Andrews, L.G., and Tollefsbol, T.O. (2003). Control mechanisms in the regulation of telomerase reverse transcriptase expression in differentiating human teratocarcinoma cells. Biochem Biophys Res Commun 306, 650–659 12810068.
[84] Martínez, P., Thanasoula, M., Mu?oz, P., Liao, C., Tejera, A., McNees, C., Flores, J.M., Fernández-Capetillo, O., Tarsounas, M., and Blasco, M.A. (2009). Increased telomere fragility and fusions resulting from TRF1 deficiency lead to degenerative pathologies and increased cancer in mice. Genes Dev 23, 2060–2075 19679647.
[85] McNees, C.J., Tejera, A.M., Martínez, P., Murga, M., Mulero, F., Fernandez-Capetillo, O., and Blasco, M.A. (2010). ATR suppresses telomere fragility and recombination but is dispensable for elongation of short telomeres by telomerase. J Cell Biol 188, 639–652 20212315.
[86] Meeker, A.K., Sommerfeld, H.J., and Coffey, D.S. (1996). Telomerase is activated in the prostate and seminal vesicles of the castrated rat. Endocrinology 137, 5743–5746 8940411.
[87] Misiti, S., Nanni, S., Fontemaggi, G., Cong, Y.S., Wen, J., Hirte, H.W., Piaggio, G., Sacchi, A., Pontecorvi, A., Bacchetti, S., (2000). Induction of hTERT expression and telomerase activity by estrogens in human ovary epithelium cells. Mol Cell Biol 20, 3764–3771 10805720.
[88] Mitchell, M., Gillis, A., Futahashi, M., Fujiwara, H., and Skordalakes, E. (2010). Structural basis for telomerase catalytic subunit TERT binding to RNA template and telomeric DNA. Nat Struct Mol Biol 17, 513–518 20357774.
[89] Moehren, U., Papaioannou, M., Reeb, C.A., Grasselli, A., Nanni, S., Asim, M., Roell, D., Prade, I., Farsetti, A., and Baniahmad, A. (2008). Wild-type but not mutant androgen receptor inhibits expression of the hTERT telomerase subunit: a novel role of AR mutation for prostate cancer development. FASEB J 22, 1258–1267 17991730.
[90] Murnane, J.P. (2010). Telomere loss as a mechanism for chromosome instability in human cancer. Cancer Res 70, 4255–4259 20484032.
[91] Nakamura, T.M., Morin, G.B., Chapman, K.B., Weinrich, S.L., Andrews, W.H., Lingner, J., Harley, C.B., and Cech, T.R. (1997). Telomerase catalytic subunit homologs from fission yeast and human. Science 277, 955–959 9252327.
[92] Nesbit, C.E., Tersak, J.M., and Prochownik, E.V. (1999). MYC oncogenes and human neoplastic disease. Oncogene 18, 3004–3016 10378696.
[93] Njajou, O.T., Cawthon, R.M., Damcott, C.M., Wu, S.H., Ott, S., Garant, M.J., Blackburn, E.H., Mitchell, B.D., Shuldiner, A.R., and Hsueh, W.C. (2007). Telomere length is paternally inherited and is associated with parental lifespan. Proc Natl Acad Sci U S A 104, 12135–12139 17623782.
[94] Njajou, O.T., Hsueh, W.C., Blackburn, E.H., Newman, A.B., Wu, S.H., Li, R., Simonsick, E.M., Harris, T.M., Cummings, S.R., and Cawthon, R.M., and the Health ABC study. (2009). Association between telomere length, specific causes of death, and years of healthy life in health, aging, and body composition, a population-based cohort study. J Gerontol A Biol Sci Med Sci 64, 860–864 19435951.
[95] Oh, S., Song, Y.H., Yim, J., and Kim, T.K. (2000). Identification of Mad as a repressor of the human telomerase (hTERT) gene. Oncogene 19, 1485–1490 10723141.
[96] Oh, W., Ghim, J., Lee, E.W., Yang, M.R., Kim, E.T., Ahn, J.H., and Song, J. (2009). PML-IV functions as a negative regulator of telomerase by interacting with TERT. J Cell Sci 122, 2613–2622 19567472.
[97] Ornish, D., Lin, J., Daubenmier, J., Weidner, G., Epel, E., Kemp, C., Magbanua, M.J., Marlin, R., Yglecias, L., Carroll, P.R., (2008). Increased telomerase activity and comprehensive lifestyle changes: a pilot study. Lancet Oncol 9, 1048–1057 18799354.
[98] Park, J.I., Venteicher, A.S., Hong, J.Y., Choi, J., Jun, S., Shkreli, M., Chang, W., Meng, Z., Cheung, P., Ji, H., (2009). Telomerase modulates Wnt signalling by association with target gene chromatin. Nature 460, 66–72 19571879.
[99] Peng, Y., Mian, I.S., and Lue, N.F. (2001). Analysis of telomerase processivity: mechanistic similarity to HIV-1 reverse transcriptase and role in telomere maintenance. Mol Cell 7, 1201–1211 11430823.
[100] Pinto, A.R., Li, H., Nicholls, C., and Liu, J.P. (2011). Telomere protein complexes and interactions with telomerase in telomere maintenance. Front Biosci 16, 187–207 21196166.
[101] Ramírez, R., Carracedo, J., Jiménez, R., Canela, A., Herrera, E., Aljama, P., and Blasco, M.A. (2003). Massive telomere loss is an early event of DNA damage-induced apoptosis. J Biol Chem 278, 836–842 12409303.
[102] Ravindranath, N., Ioffe, S.L., Marshall, G.R., Ramaswamy, S., Plant, T.M., and Dym, M. (2001). Androgen depletion activates telomerase in the prostate of the nonhuman primate, Macaca mulatta. Prostate 49, 79–89 11550213.
[103] Rochette, P.J., and Brash, D.E. (2010). Human telomeres are hypersensitive to UV-induced DNA Damage and refractory to repair. PLoS Genet 6, e100092620442874.
[104] Rudolph, K.L., Chang, S., Lee, H.W., Blasco, M., Gottlieb, G.J., Greider, C., and DePinho, R.A. (1999). Longevity, stress response, and cancer in aging telomerase-deficient mice. Cell 96, 701–712 10089885.
[105] Seimiya, H., Sawada, H., Muramatsu, Y., Shimizu, M., Ohko, K., Yamane, K., and Tsuruo, T. (2000). Involvement of 14-3-3 proteins in nuclear localization of telomerase. EMBO J 19, 2652–2661 10835362.
[106] Seth, A., and Watson, D.K. (2005). ETS transcription factors and their emerging roles in human cancer. Eur J Cancer 41, 2462–2478 16213704.
[107] Sfeir, A., Kosiyatrakul, S.T., Hockemeyer, D., MacRae, S.L., Karlseder, J., Schildkraut, C.L., and de Lange, T. (2009). Mammalian telomeres resemble fragile sites and require TRF1 for efficient replication. Cell 138, 90–103 19596237.
[108] Sharma, H.W., Sokoloski, J.A., Perez, J.R., Maltese, J.Y., Sartorelli, A.C., Stein, C.A., Nichols, G., Khaled, Z., Telang, N.T., and Narayanan, R. (1995). Differentiation of immortal cells inhibits telomerase activity. Proc Natl Acad Sci U S A 92, 12343–12346 8618897.
[109] Shay, J.W., and Bacchetti, S. (1997). A survey of telomerase activity in human cancer. Eur J Cancer 33, 787–791 9282118.
[110] 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 12717449.
[111] Soda, H., Raymond, E., Sharma, S., Lawrence, R., Davidson, K., Oka, M., Kohno, S., Izbicka, E., and Von Hoff, D.D. (2000). Effects of androgens on telomerase activity in normal and malignant prostate cells in vitro. Prostate 43, 161–168 10797490.
[112] Stewart, S.A., Hahn, W.C., O’Connor, B.F., Banner, E.N., Lundberg, A.S., Modha, P., Mizuno, H., Brooks, M.W., Fleming, M., Zimonjic, D.B., (2002). Telomerase contributes to tumorigenesis by a telomere length-independent mechanism. Proc Natl Acad Sci U S A 99, 12606–12611 12193655.
[113] Takakura, M., Kyo, S., Kanaya, T., Hirano, H., Takeda, J., Yutsudo, M., and Inoue, M. (1999). Cloning of human telomerase catalytic subunit (hTERT) gene promoter and identification of proximal core promoter sequences essential for transcriptional activation in immortalized and cancer cells. Cancer Res 59, 551–557 9973199.
[114] Takakura, M., Kyo, S., Sowa, Y., Wang, Z., Yatabe, N., Maida, Y., Tanaka, M., and Inoue, M. (2001). Telomerase activation by histone deacetylase inhibitor in normal cells. Nucleic Acids Res 29, 3006–3011 11452025.
[115] Tang, L., and Sawers, R.S. (1989). Twin pregnancy in premature ovarian failure after estrogen treatment: a case report. Am J Obstet Gynecol 161, 172–173 2502014.
[116] Teixeira, M.T., Arneric, M., Sperisen, P., and Lingner, J. (2004). Telomere length homeostasis is achieved via a switch between telomerase- extendible and -nonextendible states. Cell 117, 323–335 15109493.
[117] Terry, D.F., Nolan, V.G., Andersen, S.L., Perls, T.T., and Cawthon, R. (2008). Association of longer telomeres with better health in centenarians. J Gerontol A Biol Sci Med Sci 63, 809–812 18772468.
[118] Theimer, C.A., and Feigon, J. (2006). Structure and function of telomerase RNA. Curr Opin Struct Biol 16, 307–318 16713250.
[119] Ting, N.S., Pohorelic, B., Yu, Y., Lees-Miller, S.P., and Beattie, T.L. (2009). The human telomerase RNA component, hTR, activates the DNA-dependent protein kinase to phosphorylate heterogeneous nuclear ribonucleoprotein A1. Nucleic Acids Res 37, 6105–6115 19656952.
[120] Ting, N.S., Yu, Y., Pohorelic, B., Lees-Miller, S.P., and Beattie, T.L. (2005). Human Ku70/80 interacts directly with hTR, the RNA component of human telomerase. Nucleic Acids Res 33, 2090–2098 15824061.
[121] Tomás-Loba, A., Flores, I., Fernández-Marcos, P.J., Cayuela, M.L., Maraver, A., Tejera, A., Borrás, C., Matheu, A., Klatt, P., Flores, J.M., (2008). Telomerase reverse transcriptase delays aging in cancer-resistant mice. Cell 135, 609–622 19013273.
[122] Toogun, O.A., Dezwaan, D.C., and Freeman, B.C. (2008). The hsp90 molecular chaperone modulates multiple telomerase activities. Mol Cell Biol 28, 457–467 17954556.
[123] Toogun, O.A., Zeiger, W., and Freeman, B.C. (2007). The p23 molecular chaperone promotes functional telomerase complexes through DNA dissociation. Proc Natl Acad Sci U S A 104, 5765–5770 17389357.
[124] Ulaner, G.A., Hu, J.F., Vu, T.H., Giudice, L.C., and Hoffman, A.R. (1998). Telomerase activity in human development is regulated by human telomerase reverse transcriptase (hTERT) transcription and by alternate splicing of hTERT transcripts. Cancer Res 58, 4168–4172 9751630.
[125] Ulaner, G.A., Hu, J.F., Vu, T.H., Giudice, L.C., and Hoffman, A.R. (2001). Tissue-specific alternate splicing of human telomerase reverse transcriptase (hTERT) influences telomere lengths during human development. Int J Cancer 91, 644–649 11267974.
[126] Verdun, R.E., and Karlseder, J. (2006). The DNA damage machinery and homologous recombination pathway act consecutively to protect human telomeres. Cell 127, 709–720 17110331.
[127] Wang, J., Xie, L.Y., Allan, S., Beach, D., and Hannon, G.J. (1998). Myc activates telomerase. Genes Dev 12, 1769–1774 9637678.
[128] Wang, S., and Zhu, J. (2004). The hTERT gene is embedded in a nuclease-resistant chromatin domain. J Biol Chem 279, 55401–55410 15516693.
[129] Won, J., Yim, J., and Kim, T.K. (2002a). Opposing regulatory roles of E2F in human telomerase reverse transcriptase (hTERT) gene expression in human tumor and normal somatic cells. FASEB J 16, 1943–1945 12368233.
[130] Won, J., Yim, J., and Kim, T.K. (2002b). Sp1 and Sp3 recruit histone deacetylase to repress transcription of human telomerase reverse transcriptase (hTERT) promoter in normal human somatic cells. J Biol Chem 277, 38230–38238 12151407.
[131] Wong, J.M., and Collins, K. (2003). Telomere maintenance and disease. Lancet 362, 983–988 14511933.
[132] Wu, K.J., Grandori, C., Amacker, M., Simon-Vermot, N., Polack, A., Lingner, J., and Dalla-Favera, R. (1999). Direct activation of TERT transcription by c-MYC. Nat Genet 21, 220–224 9988278.
[133] Wymenga, L.F., Wisman, G.B., Veenstra, R., Ruiters, M.H., and Mensink, H.J. (2000). Telomerase activity in needle biopsies from prostate cancer and benign prostates. Eur J Clin Invest 30, 330–335 10759882.
[134] Xia, J., Peng, Y., Mian, I.S., and Lue, N.F. (2000). Identification of functionally important domains in the N-terminal region of telomerase reverse transcriptase. Mol Cell Biol 20, 5196–5207 10866675.
[135] Xin, H., Liu, D., Wan, M., Safari, A., Kim, H., Sun, W., O’Connor, M.S., and Songyang, Z. (2007). TPP1 is a homologue of ciliate TEBP-beta and interacts with POT1 to recruit telomerase. Nature 445, 559–562 17237767.
[136] Xu, D., Dwyer, J., Li, H., Duan, W., and Liu, J.P. (2008). Ets2 maintains hTERT gene expression and breast cancer cell proliferation by interacting with c-Myc. J Biol Chem 283, 23567–23580 18586674.
[137] Xu, D., Popov, N., Hou, M., Wang, Q., Bj?rkholm, M., Gruber, A., Menkel, A.R., and Henriksson, M. (2001). Switch from Myc/Max to Mad1/Max binding and decrease in histone acetylation at the telomerase reverse transcriptase promoter during differentiation of HL60 cells. Proc Natl Acad Sci U S A 98, 3826–3831 11274400.
[138] Yi, X., Shay, J.W., and Wright, W.E. (2001). Quantitation of telomerase components and hTERT mRNA splicing patterns in immortal human cells. Nucleic Acids Res 29, 4818–4825 11726691.
[139] Yu, C.C., Lo, S.C., and Wang, T.C. (2001). Telomerase is regulated by protein kinase C-zeta in human nasopharyngeal cancer cells. Biochem J 355, 459–464 11284734.
[140] Zaug, A.J., Podell, E.R., Nandakumar, J., and Cech, T.R. (2010). Functional interaction between telomere protein TPP1 and telomerase. Genes Dev 24, 613–622 20231318.
[141] Zhang, Q.S., Manche, L., Xu, R.M., and Krainer, A.R. (2006). hnRNP A1 associates with telomere ends and stimulates telomerase activity. RNA 12, 1116–1128 16603717.
[142] Zhang, W., Kapusta, L.R., Slingerland, J.M., and Klotz, L.H. (1998). Telomerase activity in prostate cancer, prostatic intraepithelial neoplasia, and benign prostatic epithelium. Cancer Res 58, 619–621 9485010.
[143] Zhang, X., Mar, V., Zhou, W., Harrington, L., and Robinson, M.O. (1999). Telomere shortening and apoptosis in telomerase-inhibited human tumor cells. Genes Dev 13, 2388–2399 10500096.
[144] Zinn, R.L., Pruitt, K., Eguchi, S., Baylin, S.B., and Herman, J.G. (2007). hTERT is expressed in cancer cell lines despite promoter DNA methylation by preservation of unmethylated DNA and active chromatin around the transcription start site. Cancer Res 67, 194–201 17210699.
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