Telomere-independent functions of telomerase in nuclei, cytoplasm, and mitochondria

Frontiers in Oncology

Volumn 2 SEP, Issue , 2012, Pages

  Chiodi, Ilaria ^a   Mondello, Chiara ^a  

^a CNR   (Italy)

Author keywords

Apoptosis; Cancer; Mitochondria; RNA interference; Telomerase; Telomere; TERT; Transformation

Indexed keywords

BETA CATENIN; CYCLIN D1; RNA DIRECTED DNA POLYMERASE; TELOMERASE; TELOMERASE REVERSE TRANSCRIPTASE; WNT PROTEIN;

APOPTOSIS; CELL GROWTH; CELL NUCLEUS; CELL PROLIFERATION; CYTOPLASM; GENE EXPRESSION; GENE EXPRESSION REGULATION; MITOCHONDRION; NONHUMAN; PROTEIN EXPRESSION; SHORT SURVEY; TELOMERE; UPREGULATION;

EID: 84875491664     PISSN: None     EISSN: 2234943X     Source Type: Journal    
DOI: 10.3389/fonc.2012.00133     Document Type: Short Survey

References (75)

1. Ahmed, S., Passos, J. F., Birket, M. J., Beckmann, T., Brings, S., Peters, H., et al. (2008). Telomerase does not counteract telomere shortening but protects mitochondrial function under oxidative stress. J. Cell Sci. 121, 1046-1053.
2. Artandi, S. E., Alson, S., Tietze, M. K., Sharpless, N. E., Ye, S., Greenberg, R. A., et al. (2002). Constitutive telomerase expression promotes mammary carcinomas in aging mice. Proc. Natl. Acad. Sci. U.S.A. 99, 8191-8196.
3. Barisoni, L., Mokrzycki, M., Sablay, L., Nagata, M., Yamase, H., and Mundel, P. (2000). Podocyte cell cycle regulation and proliferation in collapsing glomerulopathies. Kidney Int. 58, 137-143.
4. Barker, N., Hurlstone, A., Musisi, H., Miles, A., Bienz, M., and Clevers, H. (2001). The chromatin remodelling factor Brg-1 interacts with beta-catenin to promote target gene activation. EMBO J. 20, 4935-4943.
5. Belgiovine, C., Chiodi, I., and Mondello, C. (2008). Telomerase: cellular immortalization and neoplastic transformation. Multiple functions of a multifaceted complex. Cytogenet. Genome Res. 122, 255-262.
6. Bernardes de Jesus, B., Vera, E., Schneeberger, K., Tejera, A. M., Ayuso, E., Bosch, F., et al. (2012). Telomerase gene therapy in adult and old mice delays aging and increases longevity without increasing cancer. EMBO Mol. Med. 4, 691-704
7. Blackburn, E. H., and Gall, J. G. (1978). A tandemly repeated sequence at the termini of the extrachromosomal ribosomal RNA genes in Tetrahymena. J. Mol. Biol. 120, 33-53.
8. Bodnar, A. G., Ouellette, M., Frolkis, M., Holt, S. E., Chiu, C. P., Morin, G. B., et al. (1998). Extension of life-span by introduction of telomerase into normal human cells. Science 279, 349-352.
9. Bollmann, F. M. (2008). The many faces of telomerase: emerging extratelomeric effects. Bioessays 30, 728-732.
10. Canela, A., Martin-Caballero, J., Flores, J. M., and Blasco, M. A. (2004). Constitutive expression of tert in thymocytes leads to increased incidence and dissemination of T-cell lymphoma in Lck-Tert mice. Mol. Cell Biol. 24, 4275-4293.
11. Choi, J., Southworth, L. K., Sarin, K. Y., Venteicher, A. S., Ma, W., Chang, W., et al. (2008). TERT promotes epithelial proliferation through transcriptional control of a Myc-and Wnt-related developmental program. PLoS Genet. 4, e10. doi: 10.1371/journal.pgen.0040010
12. 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.
13. Collins, K. (2006). The biogenesis and regulation of telomerase holoenzymes. Nat. Rev. Mol. Cell Biol. 7, 484-494.
14. Cong, Y., and Shay, J. W. (2008). Actions of human telomerase beyond telomeres. Cell Res. 18, 725-732.
15. Del Bufalo, D., Rizzo, A., Trisciuoglio, D., Cardinali, G., Torrisi, M. R., Zangemeister-Wittke, U., et al. (2005). Involvement of hTERT in apoptosis induced by interference with Bcl-2 expression and function. Cell Death Differ. 12, 1429-1438.
16. Dokal, I. (2011). Dyskeratosis congenita. Hematology Am. Soc. Hematol. Educ. Program 2011, 480-486.
17. Dudognon, C., Pendino, F., Hillion, J., Saumet, A., Lanotte, M., and Segal-Bendirdjian, E. (2004). Death receptor signaling regulatory function for telomerase: hTERT abolishes TRAIL-induced apoptosis, independently of telomere maintenance. Oncogene 23, 7469-7474.
18. Flores, I., Cayuela, M. L., and Blasco, M. A. (2005). Effects of telomerase and telomere length on epidermal stem cell behavior. Science 309, 1253-1256.
19. Flores, I., and Blasco, M. A. (2010). The role of telomeres and telomerase in stem cell aging. FEBS Lett. 584, 3826-3830.
20. Geserick, C., Tejera, A., Gonzalez-Suarez, 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.
21. Gonzalez-Suarez, E., Samper, E., Ramirez, A., Flores, J. M., Martin-Caballero, J., Jorcano, J. L., et al. (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.
22. Gordon, D. M., and Santos, J. H. (2010). The emerging role of telomerase reverse transcriptase in mitochondrial DNA metabolism. J. Nucleic Acids 2010, 390791.
23. Greider, C. W., and Blackburn, E. H. (1985). Identification of a specific telomere terminal transferase activity in Tetrahymena extracts. Cell 43, 405-413.
24. Gu, B. W., Bessler, M., and Mason, P. J. (2008). A pathogenic dyskerin mutation impairs proliferation and activates a DNA damage response independent of telomere length in mice. Proc. Natl. Acad. Sci. U.S.A. 105, 10173-10178.
25. Haendeler, J., Hoffmann, J., Rahman, S., Zeiher, A. M., and Dimmeler, S. (2003). Regulation of telomerase activity and anti-apoptotic function by protein-protein interaction and phosphorylation. FEBS Lett. 536, 180-186.
26. Haendeler, J., Hoffmann, J., Zeiher, A. M., and Dimmeler, S. (2004). Antioxidant effects of statins via S-nitrosylation and activation of thioredoxin in endothelial cells: a novel vasculoprotective function of statins. Circulation 110, 856-861.
27. Haendeler, J., Drose, S., Buchner, N., Jakob, S., Altschmied, J., Goy, C., et al. (2009). Mitochondrial telomerase reverse transcriptase binds to and protects mitochondrial DNA and function from damage. Arterioscler. Thromb. Vasc. Biol. 29, 929-935.
28. Harley, C. B. (2008). Telomerase and cancer therapeutics. Nat. Rev. Cancer 8, 167-179.
29. Herschhorn, A., and Hizi, A. (2010). Retroviral reverse transcriptases. Cell Mol. Life Sci. 67, 2717-2747.
30. Hoffmeyer, K., Raggioli, A., Rudloff, S., Anton, R., Hierholzer, A., Del Valle, I., et al. (2012). Wnt/beta-catenin signaling regulates telomerase in stem cells and cancer cells. Science 336, 1549-1554.
31. Indran, I. R., Hande, M. P., and Pervaiz, S. (2010). Tumor cell redox state and mitochondria at the center of the non-canonical activity of telomerase reverse transcriptase. Mol. Aspects Med. 31, 21-28.
32. Indran, I. R., Hande, M. P., and Pervaiz, S. (2011). hTERT overexpression alleviates intracellular ROS production, improves mitochondrial function, and inhibits ROS-mediated apoptosis in cancer cells. Cancer Res. 71, 266-276.
33. Kaguni, L. S. (2004). DNA polymerase gamma, the mitochondrial replicase. Annu. Rev. Biochem. 73, 293-320.
34. Kim, M., Xu, L., and Blackburn, E. H. (2003). Catalytically active human telomerase mutants with allele-specific biological properties. Exp. Cell Res. 288, 277-287.
35. Lee, J., Sung, Y. H., Cheong, C., Choi, Y. S., Jeon, H. K., Sun, W., et al. (2008). TERT promotes cellular and organismal survival independently of telomerase activity. Oncogene 27, 3754-3760.
36. Lindvall, C., Hou, M., Komurasaki, T., Zheng, C., Henriksson, M., Sedivy, J. M., et al. (2003). Molecular characterization of human telomerase reverse transcriptase-immortalized human fibroblasts by gene expression profiling: activation of the epiregulin gene. Cancer Res. 63, 1743-1747.
37. Liu, P., and Demple, B. (2010). DNA repair in mammalian mitochondria: much more than we thought? Environ. Mol. Mutagen. 51, 417-426.
38. Lue, N. F., Bosoy, D., Moriarty, T. J., Autexier, C., Altman, B., and Leng, S. (2005). Telomerase can act as a template-and RNA-independent terminal transferase. Proc. Natl. Acad. Sci. U.S.A. 102, 9778-9783.
39. Maida, Y., Yasukawa, M., Furuuchi, M., Lassmann, T., Possemato, R., Okamoto, N., et al. (2009). An RNA-dependent RNA polymerase formed by TERT and the RMRP RNA. Nature 461, 230-235.
40. Maida, Y., and Masutomi, K. (2011). RNA-dependent RNA polymerases in RNA silencing. Biol. Chem. 392, 299-304.
41. Majerska, J., Sykorova, E., and Fajkus, J. (2011). Non-telomeric activities of telomerase. Mol. Biosyst. 7, 1013-1023.
42. Martinez, P., and Blasco, M. A. (2011). Telomeric and extra-telomeric roles for telomerase and the telomere-binding proteins. Nat. Rev. Cancer 11, 161-176.
43. Masutomi, K., Yu, E. Y., Khurts, S., Ben-Porath, I., Currier, J. L., Metz, G. B., et al. (2003). Telomerase maintains telomere structure in normal human cells. Cell 114, 241-253.
44. Masutomi, K., Possemato, R., Wong, J. M., Currier, J. L., Tothova, Z., Manola, J. B., et al. (2005). The telomerase reverse transcriptase regulates chromatin state and DNA damage responses. Proc. Natl. Acad. Sci. U.S.A. 102, 8222-8227.
45. Mondello, C., and Scovassi, A. I. (2004). Telomeres, telomerase, and apoptosis. Biochem. Cell Biol. 82, 498-507.
46. Mondello, C., Bottone, M. G., Noriki, S., Soldani, C., Pellicciari, C., and Scovassi, A. I. (2006). Oxidative stress response in telomerase-immortalized fibroblasts from a centenarian. Ann. N. Y. Acad. Sci. 1091, 94-101.
47. Moyzis, R. K., Buckingham, J. M., Cram, L. S., Dani, M., Deaven, L. L., Jones, M. D., et al. (1988). A highly conserved repetitive DNA sequence, (TTAGGG)n, present at the telomeres of human chromosomes. Proc. Natl. Acad. Sci. U.S.A. 85, 6622-6626.
48. Mukherjee, S., Firpo, E. J., Wang, Y., and Roberts, J. M. (2011). Separation of telomerase functions by reverse genetics. Proc. Natl. Acad. Sci. U.S.A. 108, E1363-E1371.
49. Okamoto, N., Yasukawa, M., Nguyen, C., Kasim, V., Maida, Y., Possemato, R., et al. (2011). Maintenance of tumor initiating cells of defined genetic composition by nucleostemin. Proc. Natl. Acad. Sci. U.S.A. 108, 20388-20393.
50. Palm, W., and de Lange, T. (2008). How shelterin protects mammalian telomeres. Annu. Rev. Genet. 42, 301-334.
51. Park, J. I., Venteicher, A. S., Hong, J. Y., Choi, J., Jun, S., Shkreli, M., et al. (2009). Telomerase modulates Wnt signalling by association with target gene chromatin. Nature 460, 66-72.
52. Reya, T., and Clevers, H. (2005). Wnt signalling in stem cells and cancer. Nature 434, 843-850.
53. Ridanpaa, M., van Eenennaam, H., Pelin, K., Chadwick, R., Johnson, C., Yuan, B., et al. (2001). Mutations in the RNA component of RNase MRP cause a pleiotropic human disease, cartilage-hair hypoplasia. Cell 104, 195-203.
54. Rodier, F., and Campisi, J. (2011). Four faces of cellular senescence. J. Cell Biol. 192, 547-556.
55. Sahin, E., Colla, S., Liesa, M., Moslehi, J., Muller, F. L., Guo, M., et al. (2011). Telomere dysfunction induces metabolic and mitochondrial compromise. Nature 470, 359-365.
56. Santos, J. H., Meyer, J. N., Skorvaga, M., Annab, L. A., and Van Houten, B. (2004). Mitochondrial hTERT exacerbates free-radical-mediated mtDNA damage. Aging Cell 3, 399-411.
57. Santos, J. H., Meyer, J. N., and Van Houten, B. (2006). Mitochondrial localization of telomerase as a determinant for hydrogen peroxide-induced mitochondrial DNA damage and apoptosis. Hum. Mol. Genet. 15, 1757-1768.
58. Saretzki, G. (2009). Telomerase, mitochondria and oxidative stress. Exp. Gerontol. 44, 485-492.
59. Sarin, K. Y., Cheung, P., Gilison, D., Lee, E., Tennen, R. I., Wang, E., et al. (2005). Conditional telomerase induction causes proliferation of hair follicle stem cells. Nature 436, 1048-1052.
60. Sharma, G. G., Gupta, A., Wang, H., Scherthan, H., Dhar, S., Gandhi, V., et al. (2003). hTERT associates with human telomeres and enhances genomic stability and DNA repair. Oncogene 22, 131-146.
61. Sharma, N. K., Reyes, A., Green, P., Caron, M. J., Bonini, M. G., Gordon, D. M., et al. (2012). Human telomerase acts as a hTR-independent reverse transcriptase in mitochondria. Nucleic Acids Res. 40, 712-725.
62. Shay, J. W., and Bacchetti, S. (1997). A survey of telomerase activity in human cancer. Eur. J. Cancer 33, 787-791.
63. Shkreli, M., Sarin, K. Y., Pech, M. F., Papeta, N., Chang, W., Brockman, S. A., et al. (2012). Reversible cell-cycle entry in adult kidney podocytes through regulated control of telomerase and Wnt signaling. Nat. Med. 18, 111-119.
64. 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.
65. Stampfer, M. R., Garbe, J., Levine, G., Lichtsteiner, S., Vasserot, A. P., and Yaswen, P. (2001). Expression of the telomerase catalytic subunit, hTERT, induces resistance to transforming growth factor beta growth inhibition in p16INK4A(-) human mammary epithelial cells. Proc. Natl. Acad. Sci. U.S.A. 98, 4498-4503.
66. Stewart, S. A., Hahn, W. C., O'Connor, B. F., Banner, E. N., Lundberg, A. S., Modha, P., et al. (2002). Telomerase contributes to tumorigenesis by a telomere length-independent mechanism. Proc. Natl. Acad. Sci. U.S.A. 99, 12606-12611.
67. Storici, F., Bebenek, K., Kunkel, T. A., Gordenin, D. A., and Resnick, M. A. (2007). RNA-templated DNA repair. Nature 447, 338-341.
68. Strong, M. A., Vidal-Cardenas, S. L., Karim, B., Yu, H., Guo, N., and Greider, C. W. (2011). Phenotypes in mTERT+/-and mTERT-/-mice are due to short telomeres, not telomere-independent functions of telomerase reverse transcriptase. Mol. Cell Biol. 31, 2369-2379.
69. Tsai, R. Y., and McKay, R. D. (2002). A nucleolar mechanism controlling cell proliferation in stem cells and cancer cells. Genes Dev. 16, 2991-3003.
70. Van Mater, D., Kolligs, F. T., Dlugosz, A. A., and Fearon, E. R. (2003). Transient activation of beta-catenin signaling in cutaneous keratinocytes is sufficient to trigger the active growth phase of the hair cycle in mice. Genes Dev. 17, 1219-1224.
71. van Steensel, B., Smogorzewska, A., and De Lange, T. (1998). TRF2 protects human telomeres from end-to-end fusions. Cell 92, 401-413.
72. Vidal-Cardenas, S. L., and Greider, C. W. (2010). Comparing effects of mTR and mTERT deletion on gene expression and DNA damage response: a critical examination of telomere length maintenance-independent roles of telomerase. Nucleic Acids Res. 38, 60-71.
73. Wege, H., Heim, D., Lütgehetmann, M., Dierlamm, J., Lohse, A. W., and Brümmendorf, T. H. (2011). Forced activation of β-catenin signaling supports the transformation of hTERT-immortalized human fetal hepatocytes. Mol. Cancer Res. 9, 1222-1231.
74. Zhang, Y., Toh, L. L., Lau, P., and Wang, P. (2012). Telomerase reverse transcriptase (TERT) is a novel target of Wnt/β-catenin pathway in human cancer. J. Biol. Chem. doi: 10.1074/jbc.M112.368282 [Epub ahead of print].
75. Zhu, J., Wang, H., Bishop, J. M., and Blackburn, E. H. (1999). Telomerase extends the lifespan of virus-transformed human cells without net telomere lengthening. Proc. Natl. Acad. Sci. U.S.A. 96, 3723-3728.