Reverzna transkriptaza telomeraze

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Reverzna transkriptaza telomeraze
Dostupne strukture
2BCK, 4B18, 4MNQ
Identifikatori
SimboliTERT; CMM9; DKCA2; DKCB4; EST2; PFBMFT1; TCS1; TP2; TRT; hEST2; hTRT
Vanjski IDOMIM187270 MGI1202709 HomoloGene31141 GeneCards: TERT Gene
EC broj2.7.7.49
Pregled RNK izražavanja
PBB GE TERT 207199 at tn.png
podaci
Ortolozi
VrstaČovekMiš
Entrez701521752
EnsemblENSG00000164362ENSMUSG00000021611
UniProtO14746O70372
Ref. Sekv. (iRNK)NM_001193376NM_009354
Ref. Sekv. (protein)NP_001180305NP_033380
Lokacija (UCSC)Chr 5:
1.25 - 1.3 Mb
Chr 13:
73.63 - 73.65 Mb
PubMed pretraga[1][2]

Reverzna transkriptaza telomeraze (TERT, ili hTERT kod ljudi) je katalitička podjedinica enzima telomeraza, koja, zajedno sa telomeraznom RNK komponentom (TERC), sačinjava najvažniju jedinicu telomeraznog kompleksa.[1][2]

Telomeraze su deo distinktne podgrupe RNK-zavisnih polimeraza. Telomeraze produžavaju telomere u DNK lancima, čime omogućavaju starećim ćelijama koje bi postale postmitotičke i podlegle apoptozi da premaše Hejflikov limit i postanu potencijalno besmrtne, kao što je to često slučaj sa ćelijama raka. Specifično, TERT je odgovoran za katalizu adicije nukleotida u TTAGGG sequenci na krajevima hromozomskih telomera.[3] Ova adicija ponavljajućih DNK sekvenci spečava degradaciju krajeva hromozoma nakon višestrukih ciklusa replikacije.[4]

hTERT odstustvo (obično usled hromozomske mutacije) je vezano za poremećaj Cri du chat.[5][6]

Interakcije[uredi - уреди | uredi izvor]

Reverzna transkriptaza telomeraze formira interakcije sa:

Reference[uredi - уреди | uredi izvor]

  1. Weinrich SL, Pruzan R, Ma L, Ouellette M, Tesmer VM, Holt SE, Bodnar AG, Lichtsteiner S, Kim NW, Trager JB, Taylor RD, Carlos R, Andrews WH, Wright WE, Shay JW, Harley CB, Morin GB (December 1997). "Reconstitution of human telomerase with the template RNA component hTR and the catalytic protein subunit hTRT". Nat. Genet. 17 (4): 498–502. PMID 9398860. doi:10.1038/ng1297-498. 
  2. Kirkpatrick KL, Mokbel K (2001). "The significance of human telomerase reverse transcriptase (hTERT) in cancer". Eur J Surg Oncol 27 (8): 754–60. PMID 11735173. doi:10.1053/ejso.2001.1151. 
  3. Shampay J, Blackburn EH (January 1988). "Generation of telomere-length heterogeneity in Saccharomyces cerevisiae". Proc. Natl. Acad. Sci. U.S.A. 85 (2): 534–8. PMC 279585. PMID 3277178. doi:10.1073/pnas.85.2.534. 
  4. Poole JC, Andrews LG, Tollefsbol TO (May 2001). "Activity, function, and gene regulation of the catalytic subunit of telomerase (hTERT)". Gene 269 (1-2): 1–12. PMID 11376932. doi:10.1016/S0378-1119(01)00440-1. 
  5. 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. PMC 1180356. PMID 12629597. doi:10.1086/374565. 
  6. Cerruti Mainardi P (2006). "Cri du Chat syndrome". Orphanet J Rare Dis 1: 33. PMC 1574300. PMID 16953888. doi:10.1186/1750-1172-1-33. 
  7. Haendeler J, Hoffmann J, Rahman S, Zeiher AM, Dimmeler S (February 2003). "Regulation of telomerase activity and anti-apoptotic function by protein-protein interaction and phosphorylation". FEBS Lett. 536 (1-3): 180–6. PMID 12586360. doi:10.1016/S0014-5793(03)00058-9. 
  8. Kawauchi K, Ihjima K, Yamada O (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. 174 (9): 5261–9. PMID 15843522. doi:10.4049/jimmunol.174.9.5261. 
  9. 9,0 9,1 Chai W, Ford LP, Lenertz L, Wright WE, Shay JW (December 2002). "Human Ku70/80 associates physically with telomerase through interaction with hTERT". J. Biol. Chem. 277 (49): 47242–7. PMID 12377759. doi:10.1074/jbc.M208542200. 
  10. Song H, Li Y, Chen G, Xing Z, Zhao J, Yokoyama KK, Li T, Zhao M (April 2004). "Human MCRS2, a cell-cycle-dependent protein, associates with LPTS/PinX1 and reduces the telomere length". Biochem. Biophys. Res. Commun. 316 (4): 1116–23. PMID 15044100. doi:10.1016/j.bbrc.2004.02.166. 
  11. Khurts S, Masutomi K, Delgermaa L, Arai K, Oishi N, Mizuno H, Hayashi N, Hahn WC, Murakami S (December 2004). "Nucleolin interacts with telomerase". J. Biol. Chem. 279 (49): 51508–15. PMID 15371412. doi:10.1074/jbc.M407643200. 
  12. Zhou XZ, Lu KP (November 2001). "The Pin2/TRF1-interacting protein PinX1 is a potent telomerase inhibitor". Cell 107 (3): 347–59. PMID 11701125. doi:10.1016/S0092-8674(01)00538-4. 
  13. Seimiya H, Sawada H, Muramatsu Y, Shimizu M, Ohko K, Yamane K, Tsuruo T (June 2000). "Involvement of 14-3-3 proteins in nuclear localization of telomerase". EMBO J. 19 (11): 2652–61. PMC 212742. PMID 10835362. doi:10.1093/emboj/19.11.2652. 

Literatura[uredi - уреди | uredi izvor]

  • 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. PMID 11322991. doi:10.1016/S0047-6374(01)00221-4. 
  • 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. PMID 15094035. doi:10.1016/S0014-5793(04)00356-4. 
  • Cristofari G, Sikora K, Lingner J (2007). "Telomerase unplugged". ACS Chem. Biol. 2 (3): 155–8. PMID 17373762. doi:10.1021/cb700037c. 
  • Beliveau A, Yaswen P (2007). "Soothing the watchman: telomerase reduces the p53-dependent cellular stress response". Cell Cycle 6 (11): 1284–7. PMID 17534147. doi:10.4161/cc.6.11.4298. 
  • 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. 

Vanjske veze[uredi - уреди | uredi izvor]