综述

端粒酶调控研究进展

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  • 军事医学科学院生物工程研究所,北京 100850
营孙阳,硕士研究生,专业方向:遗传学。Tel: 010-66931830;E-mail: 929661078@qq.com

收稿日期: 2015-08-10

  修回日期: 2015-12-14

  网络出版日期: 2016-04-20

基金资助

国家自然科学基金项目(编号:81330053)和北京市科技新星计划项目(编号:Z131102000413034)资助[Supported by the National Natural Science Foundation of China (No; 81330053) and Beijing Novo Program (No; Z131102000413034)],

Advances on the regulation of telomerase

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  • Beijing Institute of Biotechnology, Beijing 100850, China

Received date: 2015-08-10

  Revised date: 2015-12-14

  Online published: 2016-04-20

摘要

端粒酶主要包括催化组分端粒酶逆转录酶(Telomerase reverse transcriptase, TERT)和端粒酶RNA组分(Telomerase RNA component, TERC),二者与其他端粒酶复合体亚基共同组装成具有延伸端粒末端功能的全酶,在细胞衰老和肿瘤发生过程中发挥关键的作用。端粒酶调控的分子机制复杂,调控过程包括组装前各组分的转录调节、转录后调控、翻译后修饰以及亚细胞定位的调控,还包括组装过程中各组分的运输和装配的调控,以及组装后募集到端粒末端的调控。本文从以上几个方面对端粒酶的调控机制进行了综述,旨在为端粒酶相关领域的研究以及开发以端粒酶为靶点的药物奠定理论基础。

关键词: 端粒酶; 端粒; 调控

本文引用格式

营孙阳, 熊加秀, 麦洪旭, 林佳佳, 姜丽娜, 程龙, 叶棋浓 . 端粒酶调控研究进展[J]. 遗传, 2016 , 38(4) : 289 -299 . DOI: 10.16288/j.yczz.15-356

Abstract

Telomerase is composed of the catalytic subunit TERT (Telomerase reverse transcriptase),RNA subunit TERC (Telomerase RNA component) and other telomerase associated proteins. These two compartments with other telomerase subunits can assemble a holoenzyme, which maintain the length of telomeres. Telomerase plays important roles in cell senescence and tumor formation. The molecular mechanisms of the regulation of telomerase are very complicated. These processes comprise the regulation of transcription, post-transcription, post-translation and subcellular localization. Trafficking and assemble of TERT and TERC, as well as recruitment to telomeres, are also involved in this process. Here we review the regulation mechanism of telomerase from these aspects, and aim to laid a foundation for telomerase associated research and the drug targeting the telomerase.

Key words: telomerase; telomere; regulation

参考文献

[1] Palm W, de Lange T. How shelterin protects mammalian telomeres. Annu Rev Genet , 2008, 42: 301-334.
[2] O'Sullivan RJ, Karlseder J. Telomeres: protecting chromosomes against genome instability. Nat Rev Mol Cell Biol , 2010, 11(3): 171-181.
[3] Kabir S, Hockemeyer D, de Lange T. TALEN gene knockouts reveal no requirement for the conserved human shelterin protein Rap1 in telomere protection and length regulation. Cell Rep , 2014, 9(4): 1273-1280.
[4] Aeby E, Lingner J. ALT telomeres get together with nuclear receptors. Cell , 2015, 160(5): 811-813.
[5] Ly H. Genetic and environmental factors influencing human diseases with telomere dysfunction. Clin Exp Med , 2009, 2(2): 114-130.
[6] Fu D, Collins K. Purification of human telomerase complexes identifies factors involved in telomerase biogenesis and telomere length regulation. Mol Cell , 2007, 28(5): 773-785.
[7] Venteicher AS, Meng ZJ, Mason PJ, Veenstra TD, Artandi SE. Identification of ATPases pontin and reptin as telomerase components essential for holoenzyme assembly. Cell , 2008, 132(6): 945-957.
[8] Zhong F, Savage SA, Shkreli M, Giri N, Jessop L, Myers T, Chen R, Alter BP, Artandi SE. Disruption of telomerase trafficking by TCAB1 mutation causes dyskeratosis congenita. Gene Dev , 2011, 25(1): 11-16.
[9] Trochet D, Mergui X, Ivkovic I, Porreca RM, Gerbault-Seureau M, Sidibe A, Richard F, Londono-Vallejo A, Perret M, Aujard F, Riou JF. Telomere regulation during ageing and tumorigenesis of the grey mouse lemur. Biochimie , 2015, 113: 100-110.
[10] Shay JW, Wright WE. Senescence and immortalization: role of telomeres and telomerase. Carcinogenesis , 2005, 26(5): 867-874.
[11] Killela PJ, Reitman ZJ, Jiao YC, Bettegowda C, Agrawal N, Diaz LA, Jr., Friedman AH, Friedman H, Gallia GL, Giovanella BC, Grollman AP, He TC, He YP, Hruban RH, Jallo GI, Mandahl N, Meeker AK, Mertens F, Netto GJ, Ahmed Rasheed B, Riggins GJ, Rosenquist TA, Schiffman M, Shih IM, Theodorescu D, Torbenson MS, Velculescu VE, Wang TL, Wentzensen N, Wood LD, Zhang M, McLendon RE, Bigner DD, Kinzler KW, Vogelstein B, Papadopoulos N, Yan H. TERT promoter mutations occur frequently in gliomas and a subset of tumors derived from cells with low rates of self-renewal. Proc Natl Acad Sci USA , 2013, 110(15): 6021-6026.
[12] Horn S, Figl A, Sivaramakrishna Rachakonda P, Fischer C, Sucker A, Gast A, Kadel S, Moll I, Nagore E, Hemminki K, Schadendorf D, Kumar R. TERT promoter mutations in familial and sporadic melanoma. Science , 2013, 339(6122): 959-961.
[13] Kyo S, Takakura M, Fujiwara T, Inoue M. Understanding and exploiting hTERT promoter regulation for diagnosis and treatment of human cancers. Cancer Sci , 2008, 99(8): 1528-1538.
[14] Greenberg RA. Telomeres, crisis and cancer. Curr Mol Med , 2005, 5(2): 213-218.
[15] Borah S, Xi LH, Zaug AJ, Powell NM, Dancik GM, Cohen SB, Costello JC, Theodorescu D, Cech TR. TERT promoter mutations and telomerase reactivation in urothelial cancer. Science , 2015, 347(6225): 1006-1010.
[16] Lacerte A, Korah J, Roy M, Yang XJ, Lemay S, Lebrun JJ. Transforming growth factor-β inhibits telomerase through SMAD3 and E2F transcription factors. Cell Signal , 2008, 20(1): 50-59.
[17] Ballal RD, Saha T, Fan SJ, Haddad BR, Rosen EM. BRCA1 localization to the telomere and its loss from the telomere in response to DNA damage. J Biol Chem , 2009, 284(52): 36083-36098.
[18] Zhu JY, Zhao YJ, Wang SW. Chromatin and epigenetic regulation of the telomerase reverse transcriptase gene. Protein Cell , 2010, 1(1): 22-32.
[19] Wang SW, Hu CG, Zhu JY. Transcriptional silencing of a novel hTERT reporter locus during in vitro differentiation of mouse embryonic stem cells. Mol Biol Cell , 2007, 18(2): 669-677.
[20] Zhang ZX, Wang Y, Tao ZZ, Chen SM, Xiao BK, Zhou T. Subtelomeric demethylation deregulated hTERT expression, telomerase activity, and telomere length in four nasopharyngeal carcinoma c
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