人端粒酶反转录酶的生物信息学分析
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摘要
根据GenBank中注册的人端粒酶反转录酶(human telomerase reverse transcriptase, hTERT)的基因序列和氨基酸序列,通过生物信息学的方法,预测分析hTERT基因序列和氨基酸序列的组成成分、理化性质、疏水性/亲水性、跨膜结构、蛋白质二级结构、结构域和相互作用蛋白等.得出hTERT是具有完整开放阅读框且无跨膜结构的亲水性蛋白,其二级结构以α-螺旋和无规则卷曲为主,结构域含有1个端粒酶核糖核酸蛋白复合物-RNA结合域以及5个低复杂度区域;序列比对后发现与hTERT同源度最高的是大猩猩和黑猩猩,其基因序列仅相差1%;预测相互作用蛋白可知,许多蛋白如SMG6,AKT1,myc等都与hTERT有关,为hTERT的基因功能及肿瘤细胞永生化和恶性肿瘤的研究提供参考.
According to the gene sequence and amino acid sequence of human telomerase reverse transcriptase(hTERT) registered in GenBank,the composition,physicochemical properties,hydrophobicity/hydrophilicity,transmembrane structure,secondary structure of protein,domain and interacting proteins of hTERT gene sequence and amino acid sequence were predicted by bioinformatics method.The results showed that the hTERT gene is a hydrophilic protein with complete open reading frame and there isn't any transmembrane structure.The main components of its secondary structure is α-Helix and random coil.The domain contains one telomerase ribonucleoprotein complex-RNA binding and five low complexity.Sequence alignment revealed that the highest homology with hTERT is found in gorillas and chimpanzees,with only 1% difference in gene sequence.Predictive interaction proteins showed that many proteins such as SMG6,AKT1,myc are related to hTERT,which provided a reference for the study of gene function of hTERT and immortalization of cancer cells and malignant tumors.
According to the gene sequence and amino acid sequence of human telomerase reverse transcriptase(hTERT) registered in GenBank,the composition,physicochemical properties,hydrophobicity/hydrophilicity,transmembrane structure,secondary structure of protein,domain and interacting proteins of hTERT gene sequence and amino acid sequence were predicted by bioinformatics method.The results showed that the hTERT gene is a hydrophilic protein with complete open reading frame and there isn't any transmembrane structure.The main components of its secondary structure is α-Helix and random coil.The domain contains one telomerase ribonucleoprotein complex-RNA binding and five low complexity.Sequence alignment revealed that the highest homology with hTERT is found in gorillas and chimpanzees,with only 1% difference in gene sequence.Predictive interaction proteins showed that many proteins such as SMG6,AKT1,myc are related to hTERT,which provided a reference for the study of gene function of hTERT and immortalization of cancer cells and malignant tumors.
引文
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[30] PARK Y P,CHOI S C,KIM J H,et al.Up-regulation of Mac-2 binding protein by hTERT in gastric cancer[J].International Journal of Cancer,2007,120(4):813.
[31] JAGADEESH S,BANERJEE P P.Telomerase reverse transcriptase regulates the expression of a key cell cycle regulator,cyclin D1[J].Biochemical & Biophysical Research Communications,2006,347(3):774.
[32] PERRAULT S D,HORNSBY P J,BETTS D H.Global gene expression response to telomerase in bovine adrenocortical cells[J].Biochemical & Biophysical Research Communications,2005,335(3):925.
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[36] STEWART S A,HAHN W C,?CONNOR B F,et al.Telomerase contributes to tumorigenesis by a telomere length-independent mechanism[J].Proceedings of the National Academy of Sciences,2002,99(20):12606.
[37] YIN L,HUBBARD A K,GIARDINA C.NF-kappa B regulates transcription of the mouse telomerase catalytic subunit[J].Journal of Biological Chemistry,2000,275(47):36671.
[38] AKIYAMA M,HIDESHIMA T,HAYASHI T,et al.Cytokines modulate telomerase activity in a human multiple myeloma cell line[J].Cancer Research,2002,62(13):3876.
[39] ZUO Q P,LIU S K,LI Z J,et al.NF-kappa B p65 modulates the telomerase reverse transcriptase in the HepG2 hepatoma cell line[J].European Journal of Pharmacology,2011,672(1):113.
[40] ZHOU J,DING D,WANG M,et al.Telomerase reverse transcriptase in the regulation of gene expression[J].Bmb Reports,2014,47(1):8.
[2] OLOVNIKOV A M.A theory of marginotomy:the incomplete copying of template margin in enzymic synthesis of polynucleotides and biological significance of the phenomenon[J].Journal of Theoretical Biology,1973,41(1):181.
[3] 张涵渝.端粒和端粒酶结构与作用的研究进展[J].信息记录材料,2018(8):8.
[4] HARLEY C B.Telomere loss:mitotic clock or genetic time bomb?[J].Mutation Research,1991,256(2-6):271.
[5] 王建飞,曹若琼,孙阳阳,等.糖尿病患者外周血白细胞端粒酶活性变化及其影响因素分析[J].山东医药,2016,56(27):85.
[6] 魏桂芬,刘妍,李艳玲,等.人TERT对人胚胎皮质神经元损伤的保护[J].中国组织工程研究,2013,17(28):5229.
[7] 郭天姣,孙婉玲,徐娟.骨髓增生异常综合征端粒长度及其检测技术研究进展[J].白血病·淋巴瘤,2012,21(9):566.
[8] 赵盼.端粒、端粒酶及人端粒酶反转录酶在肿瘤中的研究进展[J].肿瘤研究与临床,2016,28(4):284.
[9] ZHAO X,ZHANG C,LE Z,et al.Telomerase reverse transcriptase interference synergistically promotes tumor necrosis factor-related apoptosis-inducing ligand-induced oral squamous cell carcinoma apoptosis and suppresses proliferation in vitro and in vivo[J].International Journal of Molecular Medicine,2018,42(1):1283.
[10] SAYINER A,SUREN D.Expression of human telomerase reverse transcriptase(hTERT) in thyroid neoplasms[J].Journal of the Balkan Union of Oncology,2018,23(1):229.
[11] LI G,SHEN J,CAO J,et al.Alternative splicing of human telomerase reverse transcriptase in gliomas and its modulation mediated by CX-5461[J].Journal of Experimental & Clinical Cancer Research,2018,37(1):78.
[12] KUMAGAI M,MIZUKOSHI E,TAMAI T,et al.Immune response to human telomerase reverse transcriptase-derived helper T cell epitopes in hepatocellular carcinoma patients[J].Liver International Official Journal of the International Association for the Study of the Liver,2018,38(9):1635.
[13] PAVANELLO S,CARTA A,MASTRANGELO G,et al.Relationship between telomere length,genetic traits and environmental/occupational exposures in bladder cancer risk by structural equation modelling[J].International Journal of Environmental Research & Public Health,2018,15(1):5.
[14] SHARPLESS N E,DEPINHO R A.Telomeres stem cell senescence and cancer[J].Journal of Clinical Investigation,2004,113(2):160.
[15] 李阳,孔维宝,牛世全,等.不同物种间乙酰辅酶A羧化酶的差异性和相似性[J].兰州大学学报(自然科学版),2013,49(5):682.
[16] 强毅.植物蔗糖磷酸合成酶的生物信息学分析[J].现代生物医学进展,2007(4):557.
[17] 陆小静,张振文,罗秀芹,等.木薯耐旱基因CAT的生物信息学预测与分析[J].西南农业学报,2013,26(6):2214.
[18] 任云.灰葡萄孢乳酸转运蛋白基因Bcjen1功能研究[D].杭州:浙江工业大学,2015.
[19] 袁辉,张雨良,杨峰山,等.玉米螟细胞色素P450家族CYP6AE25的克隆及序列分析[J].中国农学通报,2010,26(12):5.
[20] 郭玉琦,刘辰晖,刘桂琼,等.鸡碳酸酐酶4的生物信息学分析[J].河南农业科学,2018(5):129.
[21] 翟中和,王喜忠,丁明孝.细胞生物学[M].北京:高等教育出版社,2000.
[22] 邱思佳,霍丹群,侯长军,等.酸性蛋白酶基因Asp在红曲霉中的同源表达及序列分析[J].食品工业科技,2016,37(7):105.
[23] 孙静.高压脉冲电场对微生物生命活性和生命结构的影响[D].大连:大连工业大学,2004.
[24] 陆小静,张振文,罗秀芹,等.木薯耐旱基因CAT的生物信息学预测与分析[J].西南农业学报,2013,26(6):2214.
[25] 王廷华,邹晓莉.蛋白质理论与技术[M].北京:科学出版社,2005.
[26] 王镜岩,朱胜庚,徐长法.生物化学:上册[M].北京:高等教育出版社,2013.
[27] 杨毅,王兆松,牛瑞芳.人A1AT蛋白的生物信息学分析[J].生命科学研究,2018,22(1):42.
[28] 刘婷婷,欧阳玲.AKT和p62在外阴鳞状细胞癌变中的表达及意义[J].现代肿瘤医学,2016,24(16):2575.
[29] SMITH L L,COLLER H A,ROBERTS J M.Telomerase modulates expression of growth-controlling genes and enhances cell proliferation[J].Nature Cell Biology,2003,5(5):474.
[30] PARK Y P,CHOI S C,KIM J H,et al.Up-regulation of Mac-2 binding protein by hTERT in gastric cancer[J].International Journal of Cancer,2007,120(4):813.
[31] JAGADEESH S,BANERJEE P P.Telomerase reverse transcriptase regulates the expression of a key cell cycle regulator,cyclin D1[J].Biochemical & Biophysical Research Communications,2006,347(3):774.
[32] PERRAULT S D,HORNSBY P J,BETTS D H.Global gene expression response to telomerase in bovine adrenocortical cells[J].Biochemical & Biophysical Research Communications,2005,335(3):925.
[33] 曾辉,曹延延,王伟,等.XRCC5基因多态性与肺癌遗传易感性的相关性[J].河北医科大学学报,2009,30(10):1012.
[34] YOSHIDA G J.Emerging roles of myc in stem cell biology and novel tumor therapies[J].Journal of Experimental & Clinical Cancer Research,2018,37(1):173.
[35] TONY G,SVEN D.The hallmarks of cancer[J].Rna Biology,2012,9(6):703.
[36] STEWART S A,HAHN W C,?CONNOR B F,et al.Telomerase contributes to tumorigenesis by a telomere length-independent mechanism[J].Proceedings of the National Academy of Sciences,2002,99(20):12606.
[37] YIN L,HUBBARD A K,GIARDINA C.NF-kappa B regulates transcription of the mouse telomerase catalytic subunit[J].Journal of Biological Chemistry,2000,275(47):36671.
[38] AKIYAMA M,HIDESHIMA T,HAYASHI T,et al.Cytokines modulate telomerase activity in a human multiple myeloma cell line[J].Cancer Research,2002,62(13):3876.
[39] ZUO Q P,LIU S K,LI Z J,et al.NF-kappa B p65 modulates the telomerase reverse transcriptase in the HepG2 hepatoma cell line[J].European Journal of Pharmacology,2011,672(1):113.
[40] ZHOU J,DING D,WANG M,et al.Telomerase reverse transcriptase in the regulation of gene expression[J].Bmb Reports,2014,47(1):8.