Reverzna transkriptaza telomeraze

TERT
Available structures
PDB	Pretraga ortologa: PDBe RCSB
List of PDB id codes
	2BCK, 4B18, 4MNQ
Identifikatori
Alijasi	TERT
Spoljašnji ID	OMIM: 187270 MGI: 1202709 HomoloGene: 31141 GeneCards: TERT
Genska lokacija (miš)
Hr.	Chromosome 13 (mouse)
Kraj	73,797,962 bp
Obrazac RNK izražavanja
	More reference expression data
Genska ontologija
Molecular function	• transferase activity; • DNA binding; • nucleotidyltransferase activity; • telomeric DNA binding; • tRNA binding; • metal ion binding; • RNA-directed 5'-3' RNA polymerase activity; • telomerase RNA reverse transcriptase activity; • GO:0001948, GO:0016582 везивање за протеине плазме; • transcription coactivator binding; • telomerase RNA binding; • telomerase activity; • protein homodimerization activity; • chaperone binding; • template-free RNA nucleotidyltransferase; • RNA binding; • protein C-terminus binding; • protein N-terminus binding; • identical protein binding; • Reverzna transkriptaza; • RNA-directed DNA polymerase activity;
Cellular component	• цитоплазма; • PML body; • nuclear telomere cap complex; • RNA-directed RNA polymerase complex; • Нуклеоплазма; • хромозом; • Теломера; • telomerase catalytic core complex; • Једарце; • митохондрије; • TERT-RMRP complex; • mitochondrial nucleoid; • једро; • ћелијска мембрана; • telomerase holoenzyme complex; • цитосол; • nuclear speck;
Biological process	• positive regulation of protein localization to nucleolus; • telomere maintenance via telomerase; • DNA biosynthetic process; • regulation of protein stability; • replicative senescence; • RNA-dependent DNA biosynthetic process; • mitochondrion organization; • negative regulation of gene expression; • transcription, RNA-templated; • positive regulation of Wnt signaling pathway; • GO:0070919 production of siRNA involved in RNA interference; • positive regulation of nitric-oxide synthase activity; • establishment of protein localization to telomere; • negative regulation of production of siRNA involved in RNA interference; • DNA strand elongation; • positive regulation of protein binding; • negative regulation of extrinsic apoptotic signaling pathway in absence of ligand; • telomere maintenance; • GO:0062103 RNA biosynthetic process; • positive regulation of pri-miRNA transcription by RNA polymerase II; • negative regulation of cellular senescence; • response to cadmium ion; • positive regulation of G1/S transition of mitotic cell cycle; • beta-catenin-TCF complex assembly; • негативно регулисање апоптотичког процеса; • positive regulation of glucose import; • positive regulation of angiogenesis; • positive regulation of vascular associated smooth muscle cell migration; • negative regulation of glial cell proliferation; • positive regulation of transdifferentiation; • cellular response to hypoxia; • positive regulation of vascular associated smooth muscle cell proliferation; • negative regulation of endothelial cell apoptotic process; • GO:1904089 негативно уређење неурона процеса апоптозе; • positive regulation of hair cycle; • positive regulation of stem cell proliferation;
	Sources:Amigo / QuickGO
Ortolozi
	7015
	21752
	ENSG00000164362
	ENSMUSG00000021611
	O14746
	O70372
	NM_001193376; NM_198253; NM_198254; NM_198255
	NM_009354; NM_001362387; NM_001362388
	NP_001180305; NP_937983
	NP_033380; NP_001349316; NP_001349317
	Wikidata
View/Edit Human	View/Edit Mouse

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.^[4]^[5]

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.^[6] Ova adicija ponavljajućih DNK sekvenci spečava degradaciju krajeva hromozoma nakon višestrukih ciklusa replikacije.^[7]

hTERT odstustvo (obično usled hromozomske mutacije) je vezano za sindrom mačjeg plača.^[8]^[9]

Interakcije[уреди | уреди извор]

Reverzna transkriptaza telomeraze formira interakcije sa:

Vidi još[уреди | уреди извор]

Reference[уреди | уреди извор]

^ ^а ^б ^в GRCm38: Ensembl release 89: ENSMUSG00000021611 - Ensembl, May 2017
^ „Human PubMed Reference:”. National Center for Biotechnology Information, U.S. National Library of Medicine.
^ „Mouse PubMed Reference:”. National Center for Biotechnology Information, U.S. National Library of Medicine.
^ 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 (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.
^ 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.
^ Shampay J, Blackburn EH (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.
^ Poole JC, Andrews LG, Tollefsbol TO (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.
^ 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.
^ 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.
^ Haendeler J, Hoffmann J, Rahman S, Zeiher AM, Dimmeler S (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.
^ Kawauchi K, Ihjima K, Yamada O (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.
^ ^а ^б Chai W, Ford LP, Lenertz L, Wright WE, Shay JW (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.
^ Song H, Li Y, Chen G, Xing Z, Zhao J, Yokoyama KK, Li T, Zhao M (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.
^ Khurts S, Masutomi K, Delgermaa L, Arai K, Oishi N, Mizuno H, Hayashi N, Hahn WC, Murakami S (2004). „Nucleolin interacts with telomerase”. J. Biol. Chem. 279 (49): 51508—15. PMID 15371412. doi:10.1074/jbc.M407643200.
^ Zhou XZ, Lu KP (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.
^ Seimiya H, Sawada H, Muramatsu Y, Shimizu M, Ohko K, Yamane K, Tsuruo T (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[уреди | уреди извор]

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.

Spoljašnje veze[уреди | уреди извор]

GeneReviews/NCBI/NIH/UW entry on Dyskeratosis Congenita
GeneReviews/NCBI/NIH/UW entry on Pulmonary Fibrosis, Familial
TERT+protein,+human на US National Library of Medicine Medical Subject Headings (MeSH)

[refGRCm38Ensembl-1] а ^б ^в GRCm38: Ensembl release 89: ENSMUSG00000021611 - Ensembl, May 2017

[2] „Human PubMed Reference:”. National Center for Biotechnology Information, U.S. National Library of Medicine.

[3] „Mouse PubMed Reference:”. National Center for Biotechnology Information, U.S. National Library of Medicine.

[Weinrich-4] 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 (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.

[pmid11735173-5] 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.

[pmid3277178-6] Shampay J, Blackburn EH (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.

[pmid11376932-7] Poole JC, Andrews LG, Tollefsbol TO (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.

[pmid12629597-8] 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.

[pmid16953888-9] 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.

[pmid12586360-10] Haendeler J, Hoffmann J, Rahman S, Zeiher AM, Dimmeler S (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.

[pmid15843522-11] Kawauchi K, Ihjima K, Yamada O (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.

[pmid12377759-12] а ^б Chai W, Ford LP, Lenertz L, Wright WE, Shay JW (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.

[pmid15044100-13] Song H, Li Y, Chen G, Xing Z, Zhao J, Yokoyama KK, Li T, Zhao M (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.

[pmid15371412-14] Khurts S, Masutomi K, Delgermaa L, Arai K, Oishi N, Mizuno H, Hayashi N, Hahn WC, Murakami S (2004). „Nucleolin interacts with telomerase”. J. Biol. Chem. 279 (49): 51508—15. PMID 15371412. doi:10.1074/jbc.M407643200.

[pmid11701125-15] Zhou XZ, Lu KP (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.

[pmid10835362-16] Seimiya H, Sawada H, Muramatsu Y, Shimizu M, Ohko K, Yamane K, Tsuruo T (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.

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