Telomerase reverse transcriptase (abbreviated to TERT, or hTERT in humans) is a catalytic subunit of the enzyme telomerase.[1] Its absence (usually as a result of a chromosomal mutation) is associated with the disorder Cri du chat.[2][3]
Despite their similarities to other RNA-dependent polymerases, telomerases are part of a distinct subgroup of proteins because they are so similar to each other even when they come from diverse organisms. To wit, telomerase lengthens telomeres in DNA strands, thereby allowing senescent cells that would otherwise become postmitotic and undergo apoptosis to exceed the Hayflick limit and become potentially immortal, as is often the case with cancerous cells.
Genome-wide association studies suggest TERT is a susceptibility gene for development of many cancers, including lung cancer.[citation needed]
Telomerase is a ribonucleoprotein polymerase that maintains telomere ends by addition of the telomere repeat TTAGGG. The enzyme consists of a protein component with reverse transcriptase activity, encoded by this gene, and an RNA component that serves as a template for the telomere repeat. Telomerase expression plays a role in cellular senescence, as it is normally repressed in postnatal somatic cells, resulting in progressive shortening of telomeres. Deregulation of telomerase expression in somatic cells may be involved in oncogenesis. Studies in mice suggest that telomerase also participates in chromosomal repair, since de novo synthesis of telomere repeats may occur at double-stranded breaks. Alternatively spliced variants encoding different isoforms of telomerase reverse transcriptase have been identified; the full-length sequence of some variants has not been determined. Alternative splicing at this locus is thought to be one mechanism of regulation of telomerase activity.[4]
[edit] Interactions
Telomerase reverse transcriptase has been shown to interact with Ku70,[5] YWHAQ,[6] Nucleolin,[7] Ku80,[5] Heat shock protein 90kDa alpha (cytosolic), member A1,[8][9] MCRS1[10] and PINX1.[11]
[edit] See also
[edit] References
- ^ Kirkpatrick KL, Mokbel K (2001). "The significance of human telomerase reverse transcriptase (hTERT) in cancer". Eur J Surg Oncol 27 (8): 754–60. doi:10.1053/ejso.2001.1151. PMID 11735173.
- ^ Zhang A, Zheng C, Hou M, Lindvall C, Li KJ, Erlandsson F, Björkholm M, Gruber A, Blennow E, Xu D (2003). "Deletion of the telomerase reverse transcriptase gene and haploinsufficiency of telomere maintenance in Cri du chat syndrome". Am. J. Hum. Genet. 72 (4): 940–8. doi:10.1086/374565. PMC 1180356. PMID 12629597. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=1180356.
- ^ Cerruti Mainardi P (2006). "Cri du Chat syndrome". Orphanet J Rare Dis 1: 33. doi:10.1186/1750-1172-1-33. PMC 1574300. PMID 16953888. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=1574300.
- ^ "Entrez Gene: TERT telomerase reverse transcriptase". http://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=7015.
- ^ a b Chai, Weihang; Ford Lance P, Lenertz Lisa, Wright Woodring E, Shay Jerry W (Dec. 2002). "Human Ku70/80 associates physically with telomerase through interaction with hTERT". J. Biol. Chem. (United States) 277 (49): 47242–7. doi:10.1074/jbc.M208542200. ISSN 0021-9258. PMID 12377759.
- ^ Seimiya, H; Sawada H, Muramatsu Y, Shimizu M, Ohko K, Yamane K, Tsuruo T (Jun. 2000). "Involvement of 14-3-3 proteins in nuclear localization of telomerase". EMBO J. (ENGLAND) 19 (11): 2652–61. doi:10.1093/emboj/19.11.2652. ISSN 0261-4189. PMC 212742. PMID 10835362. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=212742.
- ^ Khurts, Shilagardi; Masutomi Kenkichi, Delgermaa Luvsanjav, Arai Kuniaki, Oishi Naoki, Mizuno Hideki, Hayashi Naoyuki, Hahn William C, Murakami Seishi (Dec. 2004). "Nucleolin interacts with telomerase". J. Biol. Chem. (United States) 279 (49): 51508–15. doi:10.1074/jbc.M407643200. ISSN 0021-9258. PMID 15371412.
- ^ Haendeler, Judith; Hoffmann Jörg, Rahman Sandy, Zeiher Andreas M, Dimmeler Stefanie (Feb. 2003). "Regulation of telomerase activity and anti-apoptotic function by protein-protein interaction and phosphorylation". FEBS Lett. (Netherlands) 536 (1–3): 180–6. doi:10.1016/S0014-5793(03)00058-9. ISSN 0014-5793. PMID 12586360.
- ^ Kawauchi, Kiyotaka; Ihjima Kimiko, Yamada Osamu (May. 2005). "IL-2 increases human telomerase reverse transcriptase activity transcriptionally and posttranslationally through phosphatidylinositol 3'-kinase/Akt, heat shock protein 90, and mammalian target of rapamycin in transformed NK cells". J. Immunol. (United States) 174 (9): 5261–9. ISSN 0022-1767. PMID 15843522.
- ^ Song, Hai; Li Yiliang, Chen Guoyuan, Xing Zhen, Zhao Jing, Yokoyama Kazunari K, Li Tsaiping, Zhao Mujun (Apr. 2004). "Human MCRS2, a cell-cycle-dependent protein, associates with LPTS/PinX1 and reduces the telomere length". Biochem. Biophys. Res. Commun. (United States) 316 (4): 1116–23. doi:10.1016/j.bbrc.2004.02.166. ISSN 0006-291X. PMID 15044100.
- ^ Zhou, X Z; Lu K P (Nov. 2001). "The Pin2/TRF1-interacting protein PinX1 is a potent telomerase inhibitor". Cell (United States) 107 (3): 347–59. doi:10.1016/S0092-8674(01)00538-4. ISSN 0092-8674. PMID 11701125.
[edit] Further reading
- Mattson MP, Fu W, Zhang P (2001). "Emerging roles for telomerase in regulating cell differentiation and survival: a neuroscientist's perspective". Mech. Ageing Dev. 122 (7): 659–71. doi:10.1016/S0047-6374(01)00221-4. PMID 11322991.
- Castillo Ureta H, Barrera Saldaña HA, Martínez Rodríguez HG (2003). "[Telomerase: an enzyme with multiple applications in cancer research]". Rev. Invest. Clin. 54 (4): 342–8. PMID 12415959.
- Janknecht R (2004). "On the road to immortality: hTERT upregulation in cancer cells". FEBS Lett. 564 (1–2): 9–13. doi:10.1016/S0014-5793(04)00356-4. PMID 15094035.
- Cristofari G, Sikora K, Lingner J (2007). "Telomerase unplugged". ACS Chem. Biol. 2 (3): 155–8. doi:10.1021/cb700037c. PMID 17373762.
- Beliveau A, Yaswen P (2007). "Soothing the watchman: telomerase reduces the p53-dependent cellular stress response". Cell Cycle 6 (11): 1284–7. doi:10.4161/cc.6.11.4298. PMID 17534147.
- Bellon M, Nicot C (2007). "Telomerase: a crucial player in HTLV-I-induced human T-cell leukemia". Cancer genomics & proteomics 4 (1): 21–5. PMID 17726237.
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Separation
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see also DNA replication and repair-deficiency disorder
B bsyn: dna ( repl, cycl, reco, repr) · tscr ( fact, tcrg, nucl, rnat, rept, ptts) · tltn ( risu, pttl, nexn) · dnab, rnab/ runp · stru ( domn, 1°, 2°, 3°, 4°)
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