Human Protection of Telomeres 1 (POT1) Is a Negative Regulator of Telomerase Activity In Vitro

Colleen Kelleher; Isabel Kurth; Joachim Lingner

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Human Protection of Telomeres 1 (POT1) Is a Negative Regulator of Telomerase Activity In Vitro

机译：端粒1（POT1）的人类保护是端粒酶活性的体外负调节剂。

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The telomeric single-strand DNA binding protein protection of telomeres 1 (POT1) protects telomeres from rapid degradation in Schizosaccharomyces pombe and has been implicated in positive and negative telomere length regulation in humans. Human POT1 appears to interact with telomeres both through direct binding to the 3′ overhanging G-strand DNA and through interaction with the TRF1 duplex telomere DNA binding complex. The influence of POT1 on telomerase activity has not been studied at the molecular level. We show here that POT1 negatively effects telomerase activity in vitro. We find that the DNA binding activity of POT1 is required for telomerase inhibition. Furthermore, POT1 is incapable of inhibiting telomeric repeat addition to substrate primers that are defective for POT1 binding, suggesting that in vivo, POT1 likely affects substrate access to telomerase.

机译：端粒1（POT1）的端粒单链DNA结合蛋白保护可以保护端粒免受 Schizosaccharomyces pombe 中的迅速降解，并参与了人类端粒长度的正负调节。人类POT1似乎通过直接结合到3'突出的G链DNA以及通过与TRF1双链体端粒DNA结合复合物的相互作用而与端粒相互作用。尚未在分子水平上研究过POT1对端粒酶活性的影响。我们在这里显示POT1在体外会对端粒酶活性产生负面影响。我们发现端粒酶抑制需要POT1的DNA结合活性。此外，POT1无法抑制端粒重复添加到对POT1结合有缺陷的底物引物上，这表明POT1在体内可能影响底物接近端粒酶。 展开▼

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《Molecular and Cellular Biology》 |2005年第2期|共11页

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Colleen Kelleher; Isabel Kurth; Joachim Lingner;
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中图分类细胞生物学;

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专利

1. Telomere 1 (POT1) gene expression and its association with telomerase activity in colorectal tumor samples with different pathological features [J] . Izgi Ahu, Gunal Armagan, Yalcin Serap, Biomedicine & pharmacotherapy =: Biomedecine & pharmacotherapie . 2014,第7期

机译：具有不同病理特征的结直肠肿瘤样本中端粒1（POT1）基因表达及其与端粒酶活性的关系

2. Human POT1 facilitates telomere elongation by telomerase [J] . Colgin LM., Baran K., Baumann P., Current Biology: CB . 2003,第11期

机译：人POT1通过端粒酶促进端粒延长

3. Telomere length, telomerase activity, and expressions of human telomerase mRNA component (hTERC) and human telomerase reverse transcriptase (hTERT) mRNA in pulmonary neuroendocrine tumors. [J] . Nishio Y, Nakanishi K, Ozeki Y, Japanese journal of clinical oncology. . 2007,第1期

机译：肺神经内分泌肿瘤的端粒长度，端粒酶活性以及人端粒酶mRNA组分（hTERC）和人端粒酶逆转录酶（hTERT）mRNA的表达。

4. The role of telomere shortening in somatic stem cells and tissue aging: lessons from telomerase model systems [C] . Stefan Tümpel, K. Lenhard Rudolph International Conference and Workshop on Hematopoietic Stem Cells . 2012

机译：端粒缩短在体细胞干细胞和组织衰老中的作用：来自端粒酶模型系统的课程

5. Conserved and Divergent Mouse and Human Telomerase and Telomere Regulation: Implications for the Development and Validation of Telomerase and Telomere-Specific Anticancer Strategies. [D] . Fakhoury, Johans. 2010

机译：保守和发散的小鼠和人类端粒酶和端粒调节：对端粒酶和端粒特异性抗癌策略的发展和验证的影响。

6. Human Protection of Telomeres 1 (POT1) Is a Negative Regulator of Telomerase Activity In Vitro [O] . Colleen Kelleher, Isabel Kurth, Joachim Lingner 2005

机译：端粒1（POT1）的人类保护是端粒酶活性的负调节剂。

7. Human Protection of Telomeres 1 (POT1) Is a Negative Regulator of Telomerase Activity In Vitro [O] . Kelleher, Colleen, Kurth, Isabel, Lingner, Joachim 2005

机译：端粒1（POT1）的人类保护是端粒酶活性的负调节剂。

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3. Protein isolated and htrt preparation, htrt protein fragment, human telomerase, isolated polynucleotide, expression vector, cell, non-human organism, isolated or recombinant antibody, processes for determining whether a compound or treatment is a modulator of an activity or expression of htrt, if a test compound is a modulator of a telomerase reverse transcriptase activity, to identify a compound that modulates htrt activity, to prepare recombinant telomerase, to detect a htrt people product in a sample and the presence of at least one telomerase positive human cell in a biological sample, to diagnose a telomerase-related condition in a patient and cancer to provide a prognosis for a cancer patient, to monitor the ability of an anti-cancer treatment, to reduce the ability proliferation of cancer cells in a patient, to increase the proliferative capacity of a vertebrate cell, to treat a condition associated with a high level of telomerase activity within a cell, to isolate a selected nu [P] . 外国专利： BR9712254A . 2000-01-18

机译：分离的蛋白和htrt制剂，htrt蛋白片段，人类端粒酶，分离的多核苷酸，表达载体，细胞，非人类有机体，分离的或重组抗体，确定化合物或治疗是否是htrt活性或表达调节剂的过程，如果受试化合物是端粒酶逆转录酶活性的调节剂，则鉴定可调节htrt活性的化合物，制备重组端粒酶，检测样品中的htrt人产物以及是否存在至少一个端粒酶阳性人类细胞生物学样品，以诊断患者和癌症中的端粒酶相关病症，为癌症患者提供预后，以监测抗癌治疗的能力，减少患者癌细胞的增殖能力，从而增加癌症患者的预后。脊椎动物细胞的增殖能力，用于治疗与细胞内端粒酶活性高水平有关的疾病，分离选定的核酸

4. Conceal Component of oligonucleotide mammal telomerase in the substantially pure form of recombinant expression plasma eukaryotic host cell process to produce a recombinant telomerase enzyme composition processes to identify polynucleotides from the telomerase component of mutant mammal mammal to identify applicant modulation agentstelomerase activity and to inhibit telomerase activity in polynucleotide human cells for gene therapy of a ribosome human disease and processes to detect the presence of a telomerase-related condition in a patient to detect the presence of a neoplastic condition in a patient and to determine the presence of telomerase rna component [P] . 外国专利： BR9508254A . 1997-12-23

机译：重组表达血浆真核宿主细胞过程的基本纯净形式的寡核苷酸哺乳动物端粒酶的隐蔽成分，以产生重组端粒酶组合物过程，以从突变哺乳动物的端粒酶成分中鉴定多核苷酸，从而鉴定申请人的调节剂端粒酶活性并抑制端粒酶活性用于核糖体人类疾病的基因治疗的多核苷酸人类细胞，以及检测患者端粒酶相关病症的存在，检测患者肿瘤性病症的存在并确定端粒酶rna组分的存在的过程

5. Preparation of isolated protein, substantially pure or recombinant, isolated trt protein, substantially pure or recombinant isolated trt protein, substantially pure or recombinant, isolated trt protein or a variant thereof, or a fragment, polynucleotide, synthetic, substantially pure or recombinant, isolated nucleic acid, encoding a trt protein, expression vector, transfected cell, non-human animal, or its progeny, transgenic non-human animal, antibody or its binding fragment, antibody, specifically immunoreactive under immunologically reactive conditions, for a trt protein or its immunogenic fragment, processes of determining whether a compound or treatment is a modulator of a trt activity or expression, of determining whether a test compound is a modulator of a trt activity, of preparing recombinant telomerase, to detect a trt gene product in a sample, to detect the presence of d and at least one telomerase positive human cell in a biological sample comprising human cells, to diagnos [P] . 外国专利： BR9711844A . 2000-01-18

机译：分离的蛋白质，基本上纯的或重组的分离的trt蛋白，基本上纯的或重组的分离的trt蛋白，基本上纯的或重组的分离的trt蛋白或其变体或片段，多核苷酸，合成的，基本上纯的或重组的分离的核酸的制备编码trt蛋白的酸，表达载体，转染的细胞，非人类动物或其后代，转基因非人类动物，抗体或其结合片段，抗体，在免疫反应条件下对trt蛋白或其免疫原具有特异性片段，确定化合物或处理是否是trt活性或表达的调节剂，确定测试化合物是否是trt活性的调节剂，制备重组端粒酶以检测样品中trt基因产物的过程，检测包含人细胞的生物样品中d和至少一种端粒酶阳性人细胞的存在，以进行诊断

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Human Protection of Telomeres 1 (POT1) Is a Negative Regulator of Telomerase Activity In Vitro

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