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1
Regulatory mechanisms of human and mouse telomerase reverse transcriptase gene transcription: distinct dependency on c-Myc.人类和小鼠端粒酶逆转录酶基因转录的调控机制:对 c-Myc 的不同依赖性。
Cytotechnology. 2010 Aug;62(4):333-9. doi: 10.1007/s10616-010-9276-y. Epub 2010 May 8.
2
Telomeric function of mammalian telomerases at short telomeres.端粒酶在短端粒上的哺乳动物端粒功能。
J Cell Sci. 2010 May 15;123(Pt 10):1693-704. doi: 10.1242/jcs.063636. Epub 2010 Apr 27.
3
Telomeres, telomerase, and myc. An update.端粒、端粒酶与原癌基因Myc。最新进展。
Mutat Res. 2000 Jan;462(1):31-47. doi: 10.1016/s1383-5742(99)00091-5.
4
Regulation of cellular immortalization and steady-state levels of the telomerase reverse transcriptase through its carboxy-terminal domain.通过其羧基末端结构域对细胞永生化和端粒酶逆转录酶稳态水平的调控。
Mol Cell Biol. 2006 Mar;26(6):2146-59. doi: 10.1128/MCB.26.6.2146-2159.2006.
5
Ad-mTERT-delta19, a conditional replication-competent adenovirus driven by the human telomerase promoter, selectively replicates in and elicits cytopathic effect in a cancer cell-specific manner.Ad-mTERT-delta19是一种由人端粒酶启动子驱动的具有条件复制能力的腺病毒,它在癌细胞中选择性复制并以癌细胞特异性方式引发细胞病变效应。
Hum Gene Ther. 2003 Oct 10;14(15):1415-28. doi: 10.1089/104303403769211637.
6
Differential cis-regulation of human versus mouse TERT gene expression in vivo: identification of a human-specific repressive element.体内人源与鼠源端粒酶逆转录酶(TERT)基因表达的差异顺式调控:一种人源特异性抑制元件的鉴定
Proc Natl Acad Sci U S A. 2005 Dec 20;102(51):18437-42. doi: 10.1073/pnas.0508964102. Epub 2005 Dec 12.
7
Inhibition of human telomerase reverse transcriptase gene expression by BRCA1 in human ovarian cancer cells.BRCA1对人卵巢癌细胞中人类端粒酶逆转录酶基因表达的抑制作用。
Biochem Biophys Res Commun. 2003 Mar 28;303(1):130-6. doi: 10.1016/s0006-291x(03)00318-8.
8
Regulation of human telomerase activity: repression by normal chromosome 3 abolishes nuclear telomerase reverse transcriptase transcripts but does not affect c-Myc activity.人类端粒酶活性的调控:正常3号染色体的抑制作用可消除细胞核端粒酶逆转录酶转录本,但不影响c-Myc活性。
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Antisense human telomerase reverse transcriptase could partially reverse malignant phenotypes of gastric carcinoma cell line in vitro.反义人端粒酶逆转录酶可在体外部分逆转胃癌细胞系的恶性表型。
Eur J Cancer Prev. 2008 Jun;17(3):209-17. doi: 10.1097/CEJ.0b013e3282b71f0d.
10
Telomerase inhibition in RenCa, a murine tumor cell line with short telomeres, by overexpression of a dominant negative mTERT mutant, reveals fundamental differences in telomerase regulation between human and murine cells.通过过表达显性负性mTERT突变体来抑制RenCa(一种端粒较短的小鼠肿瘤细胞系)中的端粒酶,揭示了人类和小鼠细胞中端粒酶调控的根本差异。
Cancer Res. 2001 Jul 15;61(14):5580-6.

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1
The transcription complex p52-ETS1 is essential for germinal center formation.转录复合物p52-ETS1对于生发中心的形成至关重要。
Nat Immunol. 2025 Jul 25. doi: 10.1038/s41590-025-02236-1.
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Iron-(Fe3+)-Dependent Reactivation of Telomerase Drives Colorectal Cancers.铁(Fe3+)依赖性端粒酶再激活驱动结直肠癌。
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TERT-Regulation and Roles in Cancer Formation.TERT 调控与癌症形成中的作用。
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4
Telomere elongation protects heart and lung tissue cells from fatal damage in rats exposed to severe hypoxia.端粒延长可保护暴露于严重缺氧环境下的大鼠心脏和肺组织细胞免受致命损伤。
J Physiol Anthropol. 2018 Feb 17;37(1):5. doi: 10.1186/s40101-018-0165-y.
5
Thymocytes maintain immune activity through telomere elongation in rats under hypoxic conditions.在低氧条件下,大鼠胸腺细胞通过端粒延长维持免疫活性。
Exp Ther Med. 2015 Nov;10(5):1877-1882. doi: 10.3892/etm.2015.2754. Epub 2015 Sep 18.
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Telomerase activated thymidine analogue pro-drug is a new molecule targeting hepatocellular carcinoma.端粒酶激活的胸苷类似物前药是一种靶向肝细胞癌的新分子。
J Hepatol. 2014 Nov;61(5):1064-72. doi: 10.1016/j.jhep.2014.05.027. Epub 2014 May 23.
7
Telomerase at the intersection of cancer and aging.端粒酶在癌症与衰老的交汇点。
Trends Genet. 2013 Sep;29(9):513-20. doi: 10.1016/j.tig.2013.06.007. Epub 2013 Jul 19.
8
Telomerase as a useful target in cancer fighting-the breast cancer case.端粒酶作为抗癌的一个有用靶点——以乳腺癌为例。
Tumour Biol. 2013 Jun;34(3):1371-80. doi: 10.1007/s13277-013-0757-4. Epub 2013 Apr 5.

本文引用的文献

1
Function of AP-1 in transcription of the telomerase reverse transcriptase gene (TERT) in human and mouse cells.AP-1在人类和小鼠细胞中端粒酶逆转录酶基因(TERT)转录中的作用。
Mol Cell Biol. 2005 Sep;25(18):8037-43. doi: 10.1128/MCB.25.18.8037-8043.2005.
2
Mechanism for the reduction of telomerase expression during muscle cell differentiation.肌肉细胞分化过程中端粒酶表达降低的机制。
J Biol Chem. 2001 Jun 22;276(25):22016-23. doi: 10.1074/jbc.M011181200. Epub 2001 Mar 28.
3
Switch from Myc/Max to Mad1/Max binding and decrease in histone acetylation at the telomerase reverse transcriptase promoter during differentiation of HL60 cells.在HL60细胞分化过程中,从Myc/Max结合转换为Mad1/Max结合,并导致端粒酶逆转录酶启动子处组蛋白乙酰化减少。
Proc Natl Acad Sci U S A. 2001 Mar 27;98(7):3826-31. doi: 10.1073/pnas.071043198.
4
Expression of the hTERT gene is regulated at the level of transcriptional initiation and repressed by Mad1.hTERT基因的表达在转录起始水平受到调控,并被Mad1抑制。
Cancer Res. 2000 Apr 15;60(8):2116-21.
5
Identification of Mad as a repressor of the human telomerase (hTERT) gene.鉴定Mad作为人类端粒酶(hTERT)基因的一种阻遏物。
Oncogene. 2000 Mar 9;19(11):1485-90. doi: 10.1038/sj.onc.1203439.
6
Sp1 cooperates with c-Myc to activate transcription of the human telomerase reverse transcriptase gene (hTERT).Sp1与c-Myc协同作用,激活人类端粒酶逆转录酶基因(hTERT)的转录。
Nucleic Acids Res. 2000 Feb 1;28(3):669-77. doi: 10.1093/nar/28.3.669.
7
Estrogen activates telomerase.雌激素激活端粒酶。
Cancer Res. 1999 Dec 1;59(23):5917-21.
8
Genomic organization and promoter characterization of the gene encoding the human telomerase reverse transcriptase (hTERT).人类端粒酶逆转录酶(hTERT)编码基因的基因组结构与启动子特征分析
Gene. 1999 May 17;232(1):97-106. doi: 10.1016/s0378-1119(99)00108-0.
9
Cloning and characterization of the promoter region of human telomerase reverse transcriptase gene.人端粒酶逆转录酶基因启动子区域的克隆与鉴定
Cancer Res. 1999 Feb 15;59(4):826-30.
10
Telomerase reverse transcriptase gene is a direct target of c-Myc but is not functionally equivalent in cellular transformation.端粒酶逆转录酶基因是c-Myc的直接靶点,但在细胞转化中功能并不等同。
Oncogene. 1999 Feb 4;18(5):1219-26. doi: 10.1038/sj.onc.1202669.

人类和小鼠端粒酶逆转录酶基因转录的调控机制:对 c-Myc 的不同依赖性。

Regulatory mechanisms of human and mouse telomerase reverse transcriptase gene transcription: distinct dependency on c-Myc.

机构信息

Department of Genetic Resources Technology, Faculty of Agriculture, Kyushu University, Fukuoka, 812-8581, Japan.

出版信息

Cytotechnology. 2010 Aug;62(4):333-9. doi: 10.1007/s10616-010-9276-y. Epub 2010 May 8.

DOI:10.1007/s10616-010-9276-y
PMID:20454928
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC2978306/
Abstract

Telomerase-a complex ribonucleoprotein enzyme-synthesizes telomeric repeats to avoid telomere loss that accompanies cell division and chromosomal replication. Expression of telomerase is detectable in embryonic cells and cancer cells, but not in normal human cells. On the other hand, in mice, substantial expression of telomerase is detected in normal cells and tissues as well as in immortalized cells. These results suggest that the regulatory mechanisms of telomerase activity in humans and mice differ. Considering these results along with the fact that the expression of the telomerase reverse transcriptase (TERT) gene is a rate-limiting step for telomerase activity, we compared transcriptional regulatory mechanisms of both the species. A series of luciferase assays and RT-PCR analyses demonstrated that c-Myc, a dominant transactivator for human TERT (hTERT), is not involved in the regulation of mouse TERT (mTERT). These results suggest that distinct molecules and pathways are involved in the process of immortalization and tumorigenesis in human and mouse cells.

摘要

端粒酶是一种复杂的核蛋白酶,可合成端粒重复序列,以避免伴随细胞分裂和染色体复制的端粒丢失。端粒酶在胚胎细胞和癌细胞中可检测到表达,但在正常人体细胞中则不能。另一方面,在小鼠中,端粒酶在正常细胞和组织以及永生化细胞中都有大量表达。这些结果表明,人类和小鼠中端粒酶活性的调控机制不同。考虑到这些结果以及端粒酶逆转录酶(TERT)基因的表达是端粒酶活性的限速步骤,我们比较了两种物种的转录调控机制。一系列荧光素酶检测和 RT-PCR 分析表明,人端粒酶(hTERT)的主要转录激活因子 c-Myc 不参与小鼠端粒酶(mTERT)的调节。这些结果表明,在人类和小鼠细胞的永生化和肿瘤发生过程中涉及不同的分子和途径。