WordNet
- an enzyme in eukaryotic cells that can add telomeres to the ends of chromosomes after they divide
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Tribolium castaneum telomerase catalytic subunit, TERT, bound to putative RNA template and telomeric DNA (PDB 3KYL)
| RNA-directed DNA polymerase | |||||||||
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A conceptual diagram showing the protein component of telomerase (TERT) in grey and the RNA component (TR) in yellow
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| EC number | 2.7.7.49 | ||||||||
| CAS number | 9068-38-6 | ||||||||
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| IntEnz | IntEnz view | ||||||||
| BRENDA | BRENDA entry | ||||||||
| ExPASy | NiceZyme view | ||||||||
| KEGG | KEGG entry | ||||||||
| MetaCyc | metabolic pathway | ||||||||
| PRIAM | profile | ||||||||
| PDB structures | RCSB PDB PDBe PDBsum | ||||||||
| Gene Ontology | AmiGO / QuickGO | ||||||||
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Telomerase, also called terminal transferase,[1] is a ribonucleoprotein that adds a species-dependent telomere repeat sequence to the 3' end of telomeres. A telomere is a region of repetitive sequences at each end of eukaryotic chromosomes in most eukaryotes. Telomeres protect the end of the chromosome from DNA damage or from fusion with neighbouring chromosomes. The fruit fly Drosophila melanogaster lacks telomerase, but instead uses retrotransposons to maintain telomeres.[2]
Telomerase is a reverse transcriptase enzyme that carries its own RNA molecule (e.g., with the sequence 3′-CCCAAUCCC-5′ in Trypanosoma brucei)[3] which is used as a template when it elongates telomeres. (Beyond unicellular organisms) Telomerase is active in normal stem cells and most cancer cells, but is normally absent from, or at very low levels in, most somatic cells.
Contents
- 1 History
- 2 Human telomerase structure
- 3 Mechanism
- 4 Clinical implications
- 4.1 Aging
- 4.1.1 Premature aging
- 4.2 Cancer
- 4.2.1 Drugs
- 4.2.2 Immunotherapy
- 4.2.3 Telomerase Vaccines
- 4.2.3.1 Targeted apoptosis
- 4.3 Heart disease, diabetes and quality of life
- 4.4 Rare human diseases
- 4.1 Aging
- 5 See also
- 6 References
- 7 Further reading
- 8 External links
History
The existence of a compensatory mechanism for telomere shortening was first found by Soviet biologist Alexey Olovnikov in 1973,[4] who also suggested the telomere hypothesis of aging and the telomere's connections to cancer.
Telomerase in the ciliate Tetrahymena was discovered by Carol W. Greider and Elizabeth Blackburn in 1984.[5] Together with Jack W. Szostak, Greider and Blackburn were awarded the 2009 Nobel Prize in Physiology or Medicine for their discovery.[6]
The role of telomeres and telomerase in cell aging and cancer was established by scientists at biotechnology company Geron with the cloning of the RNA and catalytic components of human telomerase[7] and the development of a polymerase chain reaction (PCR) based assay for telomerase activity called the TRAP assay, which surveys telomerase activity in multiple types of cancer.[8]
Human telomerase structure
The molecular composition of the human telomerase enzyme complex was determined by Dr Scott Cohen and his team at the Children's Medical Research Institute (Sydney Australia) and consists of two molecules each of human telomerase reverse transcriptase (TERT), telomerase RNA (TR or TERC), and dyskerin (DKC1).[9] The genes of telomerase subunits, which include TERT,[10] TERC,[11] DKC1[12] and TEP1,[13] are located on different chromosomes. The human TERT gene (hTERT) is translated into a protein of 1132 amino acids.[14] TERT polypeptide folds with (and carries) TERC, a non-coding RNA (451 nucleotides long). TERT has a 'mitten' structure that allows it to wrap around the chromosome to add single-stranded telomere repeats.
TERT is a reverse transcriptase, which is a class of enzyme that creates single-stranded DNA using single-stranded RNA as a template.
An image illustrating how telomerase elongates telomere ends progressively.
The protein consists of four conserved domains (RNA-Binding Domain (TRBD), fingers, palm and thumb), organized into a ring configuration that shares common features with retroviral reverse transcriptases, viral RNA polymerases and bacteriophage B-family DNA polymerases.[15][16]
TERT proteins from many eukaryotes have been sequenced.[17]
Mechanism
By using TERC, TERT can add a six-nucleotide repeating sequence, 5'-TTAGGG (in vertebrates, the sequence differs in other organisms) to the 3' strand of chromosomes. These TTAGGG repeats (with their various protein binding partners) are called telomeres. The template region of TERC is 3'-CAAUCCCAAUC-5'.[18]
Telomerase can bind the first few nucleotides of the template to the last telomere sequence on the chromosome, add a new telomere repeat (5'-GGTTAG-3') sequence, let go, realign the new 3'-end of telomere to the template, and repeat the process. Telomerase reverses telomere shortening.
Clinical implications
Aging
Telomerase replaces short bits of DNA known as telomeres, which are otherwise shortened when a cell divides via mitosis.
In normal circumstances, absent telomerase, if a cell divides recursively, at some point the progeny reach their Hayflick limit,[19] which is believed to be between 50–70 cell divisions. At the limit the cells become senescent and cell division stops.[20] Telomerase allows each offspring to replace the lost bit of DNA allowing the cell line to divide without ever reaching the limit. This same unbounded growth is a feature of cancerous growth.[21]
Embryonic stem cells express telomerase, which allows them to divide repeatedly and form the individual. In adults, telomerase is highly expressed only in cells that need to divide regularly especially in male sperm cells but also in epidermal cells,[22] in activated T cell[23] and B cell[24] lymphocytes, as well as in certain adult stem cells, but in the great majority of cases somatic cells do not express telomerase.[25]
A comparative biology study of mammalian telomeres indicated that telomere length of some mammalian species correlates inversely, rather than directly, with lifespan, and concluded that the contribution of telomere length to lifespan is unresolved.[26] Telomere shortening does not occur with age in some postmitotic tissues, such as in the rat brain.[27] In humans, skeletal muscle telomere lengths remain stable from ages 23 –74.[28] In baboon skeletal muscle, which consists of fully differentiated post-mitotic cells, less than 3% of myonuclei contain damaged telomeres and this percentage does not increase with age.[29] Thus, telomere shortening does not appear to be a major factor in the aging of the differentiated cells of brain or skeletal muscle. In human liver, cholangiocytes and hepatocytes show no age-related telomere shortening.[30] Another study found little evidence that, in humans, telomere length is a significant biomarker of normal aging with respect to important cognitive and physical abilities.[31]
Some experiments have raised questions on whether telomerase can be used as an anti-aging therapy, namely, the fact that mice with elevated levels of telomerase have higher cancer incidence and hence do not live longer. Telomerase also favors tumorogenesis, which leads to questions about its potential as an anti-aging therapy.[32] On the other hand, one study showed that activating telomerase in cancer-resistant mice by overexpressing its catalytic subunit extended lifespan.[33]
Exposure of T lymphocytes from HIV-infected human donors to a small molecule telomerase activator (TAT2) retards telomere shortening, increases proliferative potential and enhances cytokine/chemokine production and antiviral activity.[34]
A study that focused on Ashkenazi Jews found that long-lived subjects inherited a hyperactive version of telomerase.[35]
Mice engineered to block the gene that produces telomerase, unless they are given a certain drug, aged at a much faster rate, and died at about six months, instead of reaching the average mouse lifespan, about three years. Administering the drug at 6 months turned on telomerase production and caused their organs to be "rejuvenated," restored fertility, and normalized their ability to detect or process odors.[36][37]
A 2012 study reported that introducing the TERT gene into healthy one-year-old mice using an engineered adeno-associated virus led to a 24% increase in lifespan, without any increase in cancer.[38]
Premature aging
Premature aging syndromes including Werner syndrome, Ataxia telangiectasia, Ataxia-telangiectasia like disorder, Bloom syndrome, Fanconi anemia and Nijmegen breakage syndrome are associated with short telomeres.[39] However, the genes that have mutated in these diseases all have roles in the repair of DNA damage and the increased DNA damage may, itself, be a factor in the premature aging (see DNA damage theory of aging). An additional role in maintaining telomere length is an active area of investigation.
Cancer
In vitro, when cells approach the Hayflick limit, the time to senescence can be extended by inactivating the tumor suppressor proteins - p53 and Retinoblastoma protein (pRb).[citation needed] Cells that have been so-altered eventually undergo an event termed a "crisis" when the majority of the cells in the culture die. Sometimes, a cell does not stop dividing once it reaches crisis. In a typical situation, the telomeres are shortened[40] and chromosomal integrity declines with every subsequent cell division. Exposed chromosome ends are interpreted as double-stranded breaks (DSB) in DNA; such damage is usually repaired by reattaching (religating) the broken ends together. When the cell does this due to telomere-shortening, the ends of different chromosomes can be attached to each other. This solves the problem of lacking telomeres, but during cell division anaphase, the fused chromosomes are randomly ripped apart, causing many mutations and chromosomal abnormalities. As this process continues, the cell's genome becomes unstable. Eventually, either fatal damage is done to the cell's chromosomes (killing it via apoptosis), or an additional mutation that activates telomerase occurs.[citation needed]
With telomerase activation some types of cells and their offspring become immortal (bypass the Hayflick limit), thus avoiding cell death as long as the conditions for their duplication are met. Many cancer cells are considered 'immortal' because telomerase activity allows them to live much longer than any other somatic cell, which, combined with uncontrollable cell proliferation[41] is why they can form tumors. A good example of immortal cancer cells is HeLa cells, which have been used in laboratories as a model cell line since 1951.
While this method of modeling human cancer in cell culture is effective and has been used for many years by scientists, it is also very imprecise. The exact changes that allow for the formation of the tumorigenic clones in the above-described experiment are not clear. Scientists addressed this question by the serial introduction of multiple mutations present in a variety of human cancers. This has led to the identification of mutation combinations that form tumorigenic cells in a variety of cell types. While the combination varies by cell type, the following alterations are required in all cases: TERT activation, loss of p53 pathway function, loss of pRb pathway function, activation of the Ras or myc proto-oncogenes, and aberration of the PP2A protein phosphatase.[citation needed] That is to say, the cell has an activated telomerase, eliminating the process of death by chromosome instability or loss, absence of apoptosis-induction pathways, and continued mitosis activation.
This model of cancer in cell culture accurately describes the role of telomerase in actual human tumors. Telomerase activation has been observed in ~90% of all human tumors,[42] suggesting that the immortality conferred by telomerase plays a key role in cancer development. Of the tumors without TERT activation,[43] most employ a separate pathway to maintain telomere length termed Alternative Lengthening of Telomeres (ALT ).[44] The exact mechanism behind telomere maintenance in the ALT pathway is unclear, but likely involves multiple recombination events at the telomere.
Elizabeth Blackburn et al., identified the upregulation of 70 genes known or suspected in cancer growth and spread through the body, and the activation of glycolysis, which enables cancer cells to rapidly use sugar to facilitate their programmed growth rate (roughly the growth rate of a fetus).[45]
Approaches to controlling telomerase and telomeres for cancer therapy include gene therapy, immunotherapy, small-molecule and signal pathway inhibitors.[46]
Drugs
The ability to maintain functional telomeres may be one mechanism that allows cancer cells to grow in vitro for decades.[47] Telomerase activity is necessary to preserve many cancer types and is inactive in somatic cells, creating the possibility that telomerase inhibition could selectively repress cancer cell growth with minimal side effects.[48] If a drug can inhibit telomerase in cancer cells, the telomeres of successive generations will progressively shorten, limiting tumor growth.[49]
Telomerase is a good biomarker for cancer detection because most human cancers cells express high levels of it. Telomerase activity can be identified by its catalytic protein domain (hTERT). This[clarify] is the rate-limiting step in telomerase activity. It is associated with many cancer types. Various cancer cells and fibroblasts transformed with hTERT cDNA have high telomerase activity, while somatic cells do not. Cells testing positive for hTERT have positive nuclear signals. Epithelial stem cell tissue and its early daughter cells are the only noncancerous cells in which hTERT can be detected. Since hTERT expression is dependent only on the number of tumor cells within a sample, the amount of hTERT indicates the severity of a cancer.[50]
The expression of hTERT can also be used to distinguish benign tumors from malignant tumors. Malignant tumors have higher hTERT expression than benign tumors. Real-time reverse transcription polymerase chain reaction (RT-PCR) quantifying hTERT expression in various tumor samples verified this varying expression.[51]
Figure 4:A) Tumor cells expressing hTERT will actively degrade some of the protein and process for presenting. The major histocompatibility complex 1(MHC1), can then present the hTERT epitote. CD8- T cells that have antibodies against hTERT will then bind to the presented epitote. B) As a result of the antigenic binding, the T cells will release cytotoxins, which can be absorbed by the affected cell. C) These cytotoxins induce multiple proteases and results in apoptosis (or cell death).
The lack of telomerase does not affect cell growth, until the telomeres are short enough to cause cells to “die or undergo growth arrest”. However, inhibiting telomerase alone is not enough to destroy large tumors. It must be combined with surgery, radiation, chemotherapy or immunotherapy.[50]
Cells may reduce their telomere length by only 50-252 base pairs per cell division, which can lead to a long lag phase.[52][53]
Immunotherapy
Immunotherapy successfully treats some kinds of cancer, such as melanoma. This treatment involves manipulating a human’s immune system to destroy cancerous cells. Humans have two major antigen identifying lymphocytes: CD8+ cytotoxic T-lymphocytes (CTL) and CD4+ helper T-lymphocytes that can destroy cells. Antigen receptors on CTL can bind to a 9-10 amino acid chain that is presented by the major histocompatibility complex (MHC) as in Figure 4. HTERT is a potential target antigen. Immunotargeting should result in relatively few side effects since hTERT expression is associated only with telomerase and is not essential in almost all somatic cells.[54] GV1001 uses this pathway.[46] Experimental drug and vaccine therapies targeting active telomerase have been tested in mouse models, and clinical trials have begun.
In 2014 Geron Corporation received permission to resume a trial of its drug imetelstat for myelofibrosis after addressing FDA concerns over liver toxicity.[55][56] Geron licensee Merck had approval of an IND for one vaccine type.[citation needed] Imetelstat (GRN163L) binds directly to the telomerase's RNA template. One 2015 study reported that Imetelstat caused partial or complete remission in seven of 33 patients, while a second reported that it decreased blood platelet levels in all 18 study patients with essential thrombocythemia, a disorder in which the body overproduces blood platelets, increasing the risk of blood clots.[57]
Most of the harmful cancer-related effects of telomerase are dependent on an intact RNA template. Cancer stem cells that use an alternative method of telomere maintenance are still killed when telomerase's RNA template is blocked or damaged.
Telomerase Vaccines
Two telomerase vaccines have been developed: GRNVAC1 and GV1001. GRNVAC1 isolates dendritic cells and the RNA that codes for the telomerase protein and puts them back into the patient to make cytotoxic T cells that kill the telomerase-active cells. GV1001 is a peptide from the active site of hTERT and is recognized by the immune system that reacts by killing the telomerase-active cells.[46]
Targeted apoptosis
Figure 5: A) Human telomerase RNA (hTR) is present in the cell and can be targeted. B) 2-5 anti-hTR oligonucleotides is a specialized antisense oligo that can bind to the telomerase RNA. C) Once bound, the 2-5 anti-hTR oligonucleotide recruits RNase L to the sequence. Once recruited, the RNase L creates a single cleavage in the RNA (D) and causes dissociation of the RNA sequence.
Another independent approach is to use oligoadenylated anti-telomerase antisense oligonucleotides and ribozymes to target telomerase RNA, inducing dissociation and apoptosis (Figure 5). The fast induction of apoptosis through antisense binding may be a good alternative to the slower telomere shortening.[52]
Heart disease, diabetes and quality of life
Blackburn also discovered that mothers caring for very sick children have shorter telomeres when they report that their emotional stress is at a maximum and that telomerase was active at the site of blockages in coronary artery tissue, possibly accelerating heart attacks.
In 2009, it was shown that the amount of telomerase activity significantly increased following psychological stress. Across the sample of patients telomerase activity in increased peripheral blood mononuclear cells by 18% one hour after the end of the stress.[58]
E. V. Gostjeva et al. found no differences between colon cancer stem cells and fetal colon stem cells.[59]
A study in 2010 found that there was "significantly greater" telomerase activity in participants than controls after a three-month meditation retreat.[60]
Telomerase deficiency has been linked to diabetes mellitus and impaired insulin secretion in mice, due to loss of pancreatic insulin-producing cells.[61]
Rare human diseases
Mutations in TERT have been implicated in predisposing patients to aplastic anemia, a disorder in which the bone marrow fails to produce blood cells, in 2005.[62]
Cri du chat syndrome (CdCS) is a complex disorder involving the loss of the distal portion of the short arm of chromosome 5. TERT is located in the deleted region, and loss of one copy of TERT has been suggested as a cause or contributing factor of this disease.[63]
Dyskeratosis congenita (DC) is a disease of the bone marrow that can be caused by some mutations in the telomerase subunits.[64] In the DC cases, about 35% cases are X-linked-recessive on the DKC1 locus[65] and 5% cases are autosomal dominant on the TERT[66] and TERC[67] loci.
Patients with DC have severe bone marrow failure manifesting as abnormal skin pigmentation, leucoplakia (a white thickening of the oral mucosa) and nail dystrophy, as well as a variety of other symptoms. Individuals with either TERC or DKC1 mutations have shorter telomeres and defective telomerase activity in vitro versus other individuals of the same age.[68]
In one family autosomal dominant DC was linked to a heterozygous TERT mutation.[69] These patients also exhibited an increased rate of telomere-shortening, and genetic anticipation (i.e., the DC phenotype worsened with each generation).
See also
- DNA repair
- Imetelstat
- TA-65
- Telomere
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|access-date=(help) - ^ Gul, Ilhami; Dundar, Ozgur; Bodur, Serkan; Tunca, Yusuf; Tutuncu, Levent (2013). "The Status of Telomerase Enzyme Activity in Benign and Malignant Gynecologic Pathologies". Balkan Medical Journal. 30: 287–292. PMC 4115914 . PMID 25207121. doi:10.5152/balkanmedj.2013.7328.
- ^ a b Saretzki, Gabriele (2003). "Telomerase inhibition as Cancer Therapy". Cancer Letter. 194 (2): 209–219. PMID 12757979. doi:10.1016/s0304-3835(02)00708-5.
- ^ Stoyanov, V (2009). "T-loop deletion factor showing speeding aging of Homo telomere diversity and evolution". Rejuvenation Research. 12 (1): 52.
- ^ Patel, Kunal P.; Robert H., Vonderheide (2004). "Telomerase as a tumor-associated antigen for cancer immunotherapy". Cytotechnology. 45 (1–2): 91–99. PMC 3449959 . PMID 19003246. doi:10.1007/s10616-004-5132-2.
- ^ "Geron's cancer drug shakes off one FDA hold but remains on pause". FierceBiotech. Retrieved 2015-06-28.
- ^ "J&J bets up to $935M that Geron's drug can shake a checkered past". FierceBiotech. Retrieved 2015-06-28.
- ^ Johnson, Steven Ross (September 2, 2015). "Experimental blood disorder therapy shows promise in new studies". Modern Healthcare. Retrieved September 2015. Check date values in:
|access-date=(help) - ^ Epel, ES; Lin, J; Dhabhar, FS; Wolkowitz, OM; Puterman, E; Karan, L; Blackburn, EH (2010). "Dynamics of telomerase activity in response to acute psychological stress". Brain Behav Immun. 24 (4): 531–9. PMC 2856774 . PMID 20018236. doi:10.1016/j.bbi.2009.11.018.
- ^ Gostjeva, EV; Thilly, WG (2005). "Stem cell stages and the origins of colon cancer: a multidisciplinary perspective.". Stem Cell Rev. 1 (3): 243–51. PMID 17142861. doi:10.1385/SCR:1:3:243.
- ^ Jacobs TL, et al. (June 2011). "Intensive meditation training, immune cell telomerase activity, and psychological mediators.". nih.gov. 36: 664–81. PMID 21035949. doi:10.1016/j.psyneuen.2010.09.010.
- ^ Ristow, Michael (2010). "Telomerase deficiency impairs glucose metabolism and insulin secretion" (PDF). Aging. 2 (10): 650–658. PMC 2993795 . PMID 20876939.
- ^ Yamaguchi, H; Calado, RT; Ly, H; Kajigaya, S; Baerlocher, GM; Chanock, SJ; Lansdorp, PM; Young, NS (April 2005). "Mutations in TERT, the gene for telomerase reverse transcriptase, in aplastic anemia". N. Engl. J. Med. 352 (14): 1413–24. PMID 15814878. doi:10.1056/NEJMoa042980.
- ^ Zhang, A; Zheng, C; Hou, M; Lindvall, C; Li, KJ; Erlandsson, F; Björkholm, M; Gruber, A; Blennow, E; Xu, D (April 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.
- ^ Yamaguchi, H (June 2007). "Mutations of telomerase complex genes linked to bone marrow failures". J Nippon Med Sch. 74 (3): 202–9. PMID 17625368. doi:10.1272/jnms.74.202.
- ^ Heiss, NS; Knight, SW; Vulliamy, TJ; Klauck, SM; Wiemann, S; Mason, PJ; Poustka, A; Dokal, I (May 1998). "X-linked dyskeratosis congenita is caused by mutations in a highly conserved gene with putative nucleolar functions". Nat. Genet. 19 (1): 32–8. PMID 9590285. doi:10.1038/ng0598-32.
- ^ Vulliamy, TJ; Walne, A; Baskaradas, A; Mason, PJ; Marrone, A; Dokal, I (2005). "Mutations in the reverse transcriptase component of telomerase (TERT) in patients with bone marrow failure". Blood Cells Mol. Dis. 34 (3): 257–63. PMID 15885610. doi:10.1016/j.bcmd.2004.12.008.
- ^ Vulliamy, T; Marrone, A; Goldman, F; Dearlove, A; Bessler, M; Mason, PJ; Dokal, I (September 2001). "The RNA component of telomerase is mutated in autosomal dominant dyskeratosis congenita". Nature. 413 (6854): 432–5. PMID 11574891. doi:10.1038/35096585.
- ^ Marrone, A; Walne, A; Dokal, I (June 2005). "Dyskeratosis congenita: telomerase, telomeres and anticipation". Current Opinion in Genetics & Development. 15 (3): 249–57. PMID 15917199. doi:10.1016/j.gde.2005.04.004.
- ^ Armanios, M; Chen, JL; Chang, YP; Brodsky, RA; Hawkins, A; Griffin, CA; Eshleman, JR; Cohen, AR; Chakravarti, A; Hamosh, A; Greider, CW (November 2005). "Haploinsufficiency of telomerase reverse transcriptase leads to anticipation in autosomal dominant dyskeratosis congenita". Proc. Natl. Acad. Sci. U.S.A. 102 (44): 15960–4. PMC 1276104 . PMID 16247010. doi:10.1073/pnas.0508124102.
Further reading
- The Immortal Cell, by Michael D. West, Doubleday (2003) ISBN 978-0-385-50928-2
External links
- The Telomerase Database - A Web-based tool for telomerase research.
- Three-dimensional model of telomerase at MUN
- Elizabeth Blackburn's seminars: Telomeres and Telomerase
- Telomerase at the US National Library of Medicine Medical Subject Headings (MeSH)
DNA replication (comparing Prokaryotic to Eukaryotic)
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RNA-binding protein: Ribonucleoproteins
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| snRNP |
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| Vault ribonucleoprotein particles |
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Transferases: phosphorus-containing groups (EC 2.7)
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| 2.7.1-2.7.4: phosphotransferase/kinase |
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| 2.7.6: diphosphotransferase (P2O7) |
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| 2.7.7: nucleotidyltransferase (PO4-nucleoside) |
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| 2.7.8: miscellaneous |
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| 2.7.10-2.7.13: protein kinase (PO4; protein acceptor) |
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Enzymes
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| Classification |
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- Molecular and Cellular Biology portal
UpToDate Contents
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- 1. 正常な加齢 normal aging
- 2. 再生不良性貧血：病因、臨床症状および診断 aplastic anemia pathogenesis clinical manifestations and diagnosis
- 3. 特発性肺線維症の病因 pathogenesis of idiopathic pulmonary fibrosis
- 4. 小児および思春期における遺伝性再生不良性貧血 inherited aplastic anemia in children and adolescents
- 5. 黒色腫（メラノーマ）に対する遺伝的感受性 inherited susceptibility to melanoma
English Journal
- SERS assay of telomerase activity at single-cell level and colon cancer tissues via quadratic signal amplification.
- Shi M1, Zheng J2, Liu C1, Tan G1, Qing Z1, Yang S1, Yang J3, Tan Y1, Yang R4.
- Biosensors & bioelectronics.Biosens Bioelectron.2016 Mar 15;77:673-80. doi: 10.1016/j.bios.2015.10.029. Epub 2015 Oct 22.
- As an important biomarker and therapeutic target, telomerase has attracted extensive attention concerning its detection and monitoring. Recently, enzyme-assisted amplification approaches have provided useful platforms for the telomerase activity detection, however, further improvement in sensitivity
- PMID 26496221
- Exonuclease I manipulating primer-modified gold nanoparticles for colorimetric telomerase activity assay.
- Zhang L1, Zhang S2, Pan W2, Liang Q3, Song X2.
- Biosensors & bioelectronics.Biosens Bioelectron.2016 Mar 15;77:144-8. doi: 10.1016/j.bios.2015.08.045. Epub 2015 Sep 13.
- Telomerase is a widely accepted cancer biomarker. The conventional method for telomerase activity assay, the telomeric repeat amplification protocol (TRAP), is time-consuming and susceptible to contaminants. Therefore, development of simple and sensitive strategies for telomerase detection is still
- PMID 26402592
- Telomerase activity and its association with psychological stress, mental disorders, lifestyle factors and interventions: A systematic review.
- Deng W1, Cheung ST1, Tsao SW2, Wang XM1, Tiwari AF3.
- Psychoneuroendocrinology.Psychoneuroendocrinology.2016 Feb;64:150-63. doi: 10.1016/j.psyneuen.2015.11.017. Epub 2015 Nov 25.
- OBJECTIVE: To summarise and discuss the association between telomerase activity and psychological stress, mental disorders and lifestyle factors.METHOD: A systematic review was carried out to identify prospective or retrospective studies and interventions published up to June 2015 that reported asso
- PMID 26677763
Japanese Journal
- Synthesis of Heptaoxazole Macrocyclic Analogues of Telomestatin and Evaluation of Their Telomerase Inhibitory Activities
- Shibata Kazuaki,Yoshida Masahito,Takahashi Takashi [他]
- Bulletin of the Chemical Society of Japan 86(12), 1453-1465, 2013-12
- NAID 40019906820
- Oncolytic Adenovirus-Induced Autophagy: Tumor-Suppressive Effect and Molecular Basis
- Tazawa Hiroshi,Kagawa Shunsuke,Fujiwara Toshiyoshi
- Acta Medica Okayama 67(6), 333-342, 2013-12
- … We previously developed a telomerase-specific replication-competent oncolytic adenovirus, OBP-301, which induces cell lysis in tumor cells with telomerase activities. …
- NAID 120005353344
- 3S-Ba02 生物発光検出による生体成分の高感度分析(生物発光とバイオセンシングの新たな展開,シンポジウム)
- 荒川 秀俊
- 日本生物工学会大会講演要旨集 65, 169, 2013-08-25
- NAID 110009737911
Related Links
- (tə-lŏm'ə-rās', -rāz') An enzyme that preserves the length of telomeres across cell divisions in germ cells, stem cells, and most cancer cells. A kind of reverse transcriptase, telomerase is an RNA-containing enzyme that synthesizes ...
- Published online 28 November 2010 | Nature | doi:10.1038/news.2010.635 News Telomerase reverses ageing process Dramatic rejuvenation of prematurely ... Premature ageing can be reversed by reactivating an enzyme ...
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