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Gene Review

TERT  -  telomerase reverse transcriptase

Homo sapiens

Synonyms: CMM9, DKCA2, DKCB4, EST2, HEST2, ...
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Disease relevance of TERT


Psychiatry related information on TERT

  • Telomerase activity in human development is regulated by human telomerase reverse transcriptase (hTERT) transcription and by alternate splicing of hTERT transcripts [7].
  • Results showed that the performance of the smokers was more consistent with baseline measures than that of the non-smokers, which became more impaired throughout the night on a number of tasks [CFF (P < 0.005), Total Reaction Time (TRT, P < 0.05), CTT (P < 0.05) and the Reaction Time (RT) aspect of the CTT task (P < 0.0005)] [8].
  • These findings provide promising initial evidence of the utility of the TRT scale for identifying patients who may be at a high risk for unsuccessful substance abuse treatment [9].
  • The relative importance of genetic and environmental factors for neuroticism, extraversion, impulsivity, and monotony avoidance were estimated in a sample of 99 monozygotic and 229 dizygotic pairs of twins reared apart (TRA) and a matched sample of 160 monozygotic and 212 dizygotic pairs of twins reared together (TRT) [10].

High impact information on TERT


Chemical compound and disease context of TERT


Biological context of TERT


Anatomical context of TERT


Associations of TERT with chemical compounds


Physical interactions of TERT

  • We show that hTERT-mediated primer binding can be functionally uncoupled from telomerase-mediated primer extension [32].
  • Our results also identified two distinct regions of hTR that can independently bind hTERT in vitro [33].
  • In gel mobility shift and chromatin immunoprecipitation (CHIP) assays, we found that the USF suppression is through direct binding at the E-box site of hTERT promoter and rendering the effect actively [34].
  • CGK1026 inhibits the recruitment of HDAC into E2F-pocket protein complexes assembled on the hTERT promoter [35].
  • Eventually, a single copy of the exogenous hTERT gene was observed in the relatively later passage T-HME cells in which telomere length was elongated and stabilized without obvious activation of endogenous hTERT and c-Myc expression [36].
  • In vitro and in vivo analyses show that Ets2 binds to the EtsA and EtsB DNA motifs on the hTERT gene promoter [37].

Enzymatic interactions of TERT


Co-localisations of TERT

  • Third, immunolocalization experiments demonstrate that KIP is a nuclear protein that co-localizes with hTERT in cells [39].

Regulatory relationships of TERT

  • However, the transcription rate of hTR is greatly increased in cells expressing endogenous hTERT, suggesting some overlap in transcriptional regulatory control [40].
  • Activation of telomerase is tightly regulated at the transcriptional level of the telomerase catalytic subunit [human telomerase reverse transcriptase, (hTERT)] [41].
  • Sp1 and Sp3 recruit histone deacetylase to repress transcription of human telomerase reverse transcriptase (hTERT) promoter in normal human somatic cells [42].
  • Furthermore, detection of TERT in activated satellite cells identified them as VEGF targets during muscle regeneration [43].
  • Addition of exogenous USF1 or USF2 repressed activation of the TERT promoter by E6, dependent on the proximal E box [44].
  • We assume that TAK1 triggers the repression mechanisms of the hTERT gene as a result of evoking cellular senescence programs [45].

Other interactions of TERT

  • A significant correlation between hTRT expression and telomerase activity was observed [46].
  • Reconstitution of human telomerase with the template RNA component hTR and the catalytic protein subunit hTRT [47].
  • Suppression of TERT promoter and c-Myc activity required the amino terminus of BRCA1 but not the carboxyl terminus [48].
  • Accordingly, wild-type L-Myc is much less efficient in TRRAP binding, activation of the silent TERT gene, and transformation of primary fibroblasts [49].
  • Moreover, suppression of hTERT expression was also mediated by endogenous p73 after activation of E2F1 in H1299ER-E2F1 cells [50].
  • TERT-mediated immunoprecipitation of PML or the 553-633 fragment demonstrated that these interactions inhibited telomerase activity [51].

Analytical, diagnostic and therapeutic context of TERT


  1. Use of human tissue to assess the oncogenic activity of melanoma-associated mutations. Chudnovsky, Y., Adams, A.E., Robbins, P.B., Lin, Q., Khavari, P.A. Nat. Genet. (2005) [Pubmed]
  2. Induction of cytotoxic T cell responses and tumor immunity against unrelated tumors using telomerase reverse transcriptase RNA transfected dendritic cells. Nair, S.K., Heiser, A., Boczkowski, D., Majumdar, A., Naoe, M., Lebkowski, J.S., Vieweg, J., Gilboa, E. Nat. Med. (2000) [Pubmed]
  3. Telomerase reverse transcriptase promotes cardiac muscle cell proliferation, hypertrophy, and survival. Oh, H., Taffet, G.E., Youker, K.A., Entman, M.L., Overbeek, P.A., Michael, L.H., Schneider, M.D. Proc. Natl. Acad. Sci. U.S.A. (2001) [Pubmed]
  4. Distinct dosage requirements for the maintenance of long and short telomeres in mTert heterozygous mice. Erdmann, N., Liu, Y., Harrington, L. Proc. Natl. Acad. Sci. U.S.A. (2004) [Pubmed]
  5. Telomerase expression predicts unfavorable outcome in osteosarcoma. Sanders, R.P., Drissi, R., Billups, C.A., Daw, N.C., Valentine, M.B., Dome, J.S. J. Clin. Oncol. (2004) [Pubmed]
  6. Combination of hTERT knockdown and IFN-gamma treatment inhibited angiogenesis and tumor progression in glioblastoma. George, J., Banik, N.L., Ray, S.K. Clin. Cancer Res. (2009) [Pubmed]
  7. Telomerase activity in human development is regulated by human telomerase reverse transcriptase (hTERT) transcription and by alternate splicing of hTERT transcripts. Ulaner, G.A., Hu, J.F., Vu, T.H., Giudice, L.C., Hoffman, A.R. Cancer Res. (1998) [Pubmed]
  8. The effects of cigarette smoking on overnight performance. Parkin, C., Fairweather, D.B., Shamsi, Z., Stanley, N., Hindmarch, I. Psychopharmacology (Berl.) (1998) [Pubmed]
  9. Adherence to substance abuse treatment: clinical utility of two MMPI-2 scales. Gilmore, J.D., Lash, S.J., Foster, M.A., Blosser, S.L. Journal of personality assessment. (2001) [Pubmed]
  10. Neuroticism, extraversion, and related traits in adult twins reared apart and reared together. Pedersen, N.L., Plomin, R., McClearn, G.E., Friberg, L. Journal of personality and social psychology. (1988) [Pubmed]
  11. Recombination and the Tel1 and Mec1 checkpoints differentially effect genome rearrangements driven by telomere dysfunction in yeast. Pennaneach, V., Kolodner, R.D. Nat. Genet. (2004) [Pubmed]
  12. Telomerase maintains telomere structure in normal human cells. Masutomi, K., Yu, E.Y., Khurts, S., Ben-Porath, I., Currier, J.L., Metz, G.B., Brooks, M.W., Kaneko, S., Murakami, S., DeCaprio, J.A., Weinberg, R.A., Stewart, S.A., Hahn, W.C. Cell (2003) [Pubmed]
  13. Multiple tumor suppressor pathways negatively regulate telomerase. Lin, S.Y., Elledge, S.J. Cell (2003) [Pubmed]
  14. Inositol hexaphosphate represses telomerase activity and translocates TERT from the nucleus in mouse and human prostate cancer cells via the deactivation of Akt and PKCalpha. Jagadeesh, S., Banerjee, P.P. Biochem. Biophys. Res. Commun. (2006) [Pubmed]
  15. RNA expression of human telomerase subunits TR and TERT is differentially affected by melatonin receptor agonists in the MCF-7 tumor cell line. Leon-Blanco, M.M., Guerrero, J.M., Reiter, R.J., Pozo, D. Cancer Lett. (2004) [Pubmed]
  16. Progesterone regulates human telomerase reverse transcriptase gene expression via activation of mitogen-activated protein kinase signaling pathway. Wang, Z., Kyo, S., Takakura, M., Tanaka, M., Yatabe, N., Maida, Y., Fujiwara, M., Hayakawa, J., Ohmichi, M., Koike, K., Inoue, M. Cancer Res. (2000) [Pubmed]
  17. Demethylating reagent 5-azacytidine inhibits telomerase activity in human prostate cancer cells through transcriptional repression of hTERT. Kitagawa, Y., Kyo, S., Takakura, M., Kanaya, T., Koshida, K., Namiki, M., Inoue, M. Clin. Cancer Res. (2000) [Pubmed]
  18. Activation of telomerase in BeWo cells by estrogen and 2,3,7,8-tetrachlorodibenzo-p-dioxin in co-operation with c-Myc. Sarkar, P., Shiizaki, K., Yonemoto, J., Sone, H. Int. J. Oncol. (2006) [Pubmed]
  19. Telomerase-deficient mice with short telomeres are resistant to skin tumorigenesis. González-Suárez, E., Samper, E., Flores, J.M., Blasco, M.A. Nat. Genet. (2000) [Pubmed]
  20. Direct activation of TERT transcription by c-MYC. Wu, K.J., Grandori, C., Amacker, M., Simon-Vermot, N., Polack, A., Lingner, J., Dalla-Favera, R. Nat. Genet. (1999) [Pubmed]
  21. Telomerase: biochemical considerations for enzyme and substrate. Kelleher, C., Teixeira, M.T., Förstemann, K., Lingner, J. Trends Biochem. Sci. (2002) [Pubmed]
  22. Involvement of 14-3-3 proteins in nuclear localization of telomerase. Seimiya, H., Sawada, H., Muramatsu, Y., Shimizu, M., Ohko, K., Yamane, K., Tsuruo, T. EMBO J. (2000) [Pubmed]
  23. Expression of TERT in early premalignant lesions and a subset of cells in normal tissues. Kolquist, K.A., Ellisen, L.W., Counter, C.M., Meyerson, M., Tan, L.K., Weinberg, R.A., Haber, D.A., Gerald, W.L. Nat. Genet. (1998) [Pubmed]
  24. Regulation of cellular immortalization and steady-state levels of the telomerase reverse transcriptase through its carboxy-terminal domain. Middleman, E.J., Choi, J., Venteicher, A.S., Cheung, P., Artandi, S.E. Mol. Cell. Biol. (2006) [Pubmed]
  25. Transfer of the human telomerase reverse transcriptase (TERT) gene into T lymphocytes results in extension of replicative potential. Rufer, N., Migliaccio, M., Antonchuk, J., Humphries, R.K., Roosnek, E., Lansdorp, P.M. Blood (2001) [Pubmed]
  26. Hydrogen peroxide triggers nuclear export of telomerase reverse transcriptase via Src kinase family-dependent phosphorylation of tyrosine 707. Haendeler, J., Hoffmann, J., Brandes, R.P., Zeiher, A.M., Dimmeler, S. Mol. Cell. Biol. (2003) [Pubmed]
  27. Direct activation of telomerase by EGF through Ets-mediated transactivation of TERT via MAP kinase signaling pathway. Maida, Y., Kyo, S., Kanaya, T., Wang, Z., Yatabe, N., Tanaka, M., Nakamura, M., Ohmichi, M., Gotoh, N., Murakami, S., Inoue, M. Oncogene (2002) [Pubmed]
  28. Estrogen reduces endothelial progenitor cell senescence through augmentation of telomerase activity. Imanishi, T., Hano, T., Nishio, I. J. Hypertens. (2005) [Pubmed]
  29. Regulation of telomerase activity and anti-apoptotic function by protein-protein interaction and phosphorylation. Haendeler, J., Hoffmann, J., Rahman, S., Zeiher, A.M., Dimmeler, S. FEBS Lett. (2003) [Pubmed]
  30. Both estrogen and raloxifene protect against beta-amyloid-induced neurotoxicity in estrogen receptor alpha-transfected PC12 cells by activation of telomerase activity via Akt cascade. Du, B., Ohmichi, M., Takahashi, K., Kawagoe, J., Ohshima, C., Igarashi, H., Mori-Abe, A., Saitoh, M., Ohta, T., Ohishi, A., Doshida, M., Tezuka, N., Takahashi, T., Kurachi, H. J. Endocrinol. (2004) [Pubmed]
  31. Human telomerase reverse transcriptase activated by E6 oncoprotein is required for human papillomavirus-16/18-infected lung tumorigenesis. Cheng, Y.W., Wu, T.C., Chen, C.Y., Chou, M.C., Ko, J.L., Lee, H. Clin. Cancer Res. (2008) [Pubmed]
  32. Characterization of physical and functional anchor site interactions in human telomerase. Wyatt, H.D., Lobb, D.A., Beattie, T.L. Mol. Cell. Biol. (2007) [Pubmed]
  33. Functional regions of human telomerase reverse transcriptase and human telomerase RNA required for telomerase activity and RNA-protein interactions. Bachand, F., Autexier, C. Mol. Cell. Biol. (2001) [Pubmed]
  34. Upstream stimulatory factor (USF) as a transcriptional suppressor of human telomerase reverse transcriptase (hTERT) in oral cancer cells. Chang, J.T., Yang, H.T., Wang, T.C., Cheng, A.J. Mol. Carcinog. (2005) [Pubmed]
  35. Small-molecule-based identification of dynamic assembly of E2F-pocket protein-histone deacetylase complex for telomerase regulation in human cells. Won, J., Chang, S., Oh, S., Kim, T.K. Proc. Natl. Acad. Sci. U.S.A. (2004) [Pubmed]
  36. Events in the immortalizing process of primary human mammary epithelial cells by the catalytic subunit of human telomerase. Kim, H., Farris, J., Christman, S.A., Kong, B.W., Foster, L.K., O'Grady, S.M., Foster, D.N. Biochem. J. (2002) [Pubmed]
  37. Ets2 maintains hTERT gene expression and breast cancer cell proliferation by interacting with c-Myc. Xu, D., Dwyer, J., Li, H., Duan, W., Liu, J.P. J. Biol. Chem. (2008) [Pubmed]
  38. hTERT phosphorylation by PKC is essential for telomerase holoprotein integrity and enzyme activity in head neck cancer cells. Chang, J.T., Lu, Y.C., Chen, Y.J., Tseng, C.P., Chen, Y.L., Fang, C.W., Cheng, A.J. Br. J. Cancer (2006) [Pubmed]
  39. DNA-protein kinase catalytic subunit-interacting protein KIP binds telomerase by interacting with human telomerase reverse transcriptase. Lee, G.E., Yu, E.Y., Cho, C.H., Lee, J., Muller, M.T., Chung, I.K. J. Biol. Chem. (2004) [Pubmed]
  40. Both transcriptional and posttranscriptional mechanisms regulate human telomerase template RNA levels. Yi, X., Tesmer, V.M., Savre-Train, I., Shay, J.W., Wright, W.E. Mol. Cell. Biol. (1999) [Pubmed]
  41. Treatment of malignant glioma cells with the transfer of constitutively active caspase-6 using the human telomerase catalytic subunit (human telomerase reverse transcriptase) gene promoter. Komata, T., Kondo, Y., Kanzawa, T., Hirohata, S., Koga, S., Sumiyoshi, H., Srinivasula, S.M., Barna, B.P., Germano, I.M., Takakura, M., Inoue, M., Alnemri, E.S., Shay, J.W., Kyo, S., Kondo, S. Cancer Res. (2001) [Pubmed]
  42. Sp1 and Sp3 recruit histone deacetylase to repress transcription of human telomerase reverse transcriptase (hTERT) promoter in normal human somatic cells. Won, J., Yim, J., Kim, T.K. J. Biol. Chem. (2002) [Pubmed]
  43. Telomerase mediates vascular endothelial growth factor-dependent responsiveness in a rat model of hind limb ischemia. Zaccagnini, G., Gaetano, C., Della Pietra, L., Nanni, S., Grasselli, A., Mangoni, A., Benvenuto, R., Fabrizi, M., Truffa, S., Germani, A., Moretti, F., Pontecorvi, A., Sacchi, A., Bacchetti, S., Capogrossi, M.C., Farsetti, A. J. Biol. Chem. (2005) [Pubmed]
  44. Human papillomavirus type 16 E6 activates TERT gene transcription through induction of c-Myc and release of USF-mediated repression. McMurray, H.R., McCance, D.J. J. Virol. (2003) [Pubmed]
  45. TAK1 represses transcription of the human telomerase reverse transcriptase gene. Fujiki, T., Miura, T., Maura, M., Shiraishi, H., Nishimura, S., Imada, Y., Uehara, N., Tashiro, K., Shirahata, S., Katakura, Y. Oncogene (2007) [Pubmed]
  46. Telomerase activation by hTRT in human normal fibroblasts and hepatocellular carcinomas. Nakayama, J., Tahara, H., Tahara, E., Saito, M., Ito, K., Nakamura, H., Nakanishi, T., Tahara, E., Ide, T., Ishikawa, F. Nat. Genet. (1998) [Pubmed]
  47. Reconstitution of human telomerase with the template RNA component hTR and the catalytic protein subunit hTRT. Weinrich, S.L., Pruzan, R., Ma, L., Ouellette, M., Tesmer, V.M., Holt, S.E., Bodnar, A.G., Lichtsteiner, S., Kim, N.W., Trager, J.B., Taylor, R.D., Carlos, R., Andrews, W.H., Wright, W.E., Shay, J.W., Harley, C.B., Morin, G.B. Nat. Genet. (1997) [Pubmed]
  48. BRCA1 inhibition of telomerase activity in cultured cells. Xiong, J., Fan, S., Meng, Q., Schramm, L., Wang, C., Bouzahza, B., Zhou, J., Zafonte, B., Goldberg, I.D., Haddad, B.R., Pestell, R.G., Rosen, E.M. Mol. Cell. Biol. (2003) [Pubmed]
  49. TRRAP-dependent and TRRAP-independent transcriptional activation by Myc family oncoproteins. Nikiforov, M.A., Chandriani, S., Park, J., Kotenko, I., Matheos, D., Johnsson, A., McMahon, S.B., Cole, M.D. Mol. Cell. Biol. (2002) [Pubmed]
  50. C-terminal p73 isoforms repress transcriptional activity of the human telomerase reverse transcriptase (hTERT) promoter. Racek, T., Mise, N., Li, Z., Stoll, A., Pützer, B.M. J. Biol. Chem. (2005) [Pubmed]
  51. PML-IV functions as a negative regulator of telomerase by interacting with TERT. Oh, W., Ghim, J., Lee, E.W., Yang, M.R., Kim, E.T., Ahn, J.H., Song, J. J. Cell. Sci. (2009) [Pubmed]
  52. Template definition by Tetrahymena telomerase reverse transcriptase. Miller, M.C., Liu, J.K., Collins, K. EMBO J. (2000) [Pubmed]
  53. Functional multimerization of human telomerase requires an RNA interaction domain in the N terminus of the catalytic subunit. Moriarty, T.J., Huard, S., Dupuis, S., Autexier, C. Mol. Cell. Biol. (2002) [Pubmed]
  54. Tetrahymena telomerase is active as a monomer. Bryan, T.M., Goodrich, K.J., Cech, T.R. Mol. Biol. Cell (2003) [Pubmed]
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