• Molecules and Cells
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• 제41권7호
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• pp.684-694
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• 2018

Upregulation of human telomerase reverse transcriptase (hTERT) expression is an important factor in the cellular survival and cancer. Although growing evidence suggests that hTERT inhibits cellular apoptosis by telomere-independent functions, the mechanisms involved are not fully understood. Here, we show that hTERT contains a BH3-like motif, a short peptide sequence found in BCL-2 family proteins, and interacts with anti-apoptotic BCL-2 family proteins MCL-1 and BCL-xL, suggesting a functional link between hTERT and the mitochondrial pathway of apoptosis. Additionally, we propose that hTERT can be categorized into the atypical BH3-only proteins that promote cellular survival, possibly due to the non-canonical interaction between hTERT and antiapoptotic proteins. Although the detailed mechanisms underlying the hTERT BH3-like motif functions and interactions between hTERT and BCL-2 family proteins have not been elucidated, this work proposes a possible connection between hTERT and BCL-2 family members and reconsiders the role of the BH3-like motif as an interaction motif.

• Journal of Microbiology and Biotechnology
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• 제13권4호
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• pp.517-521
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• 2003

Telomerase is a ribonucleoprotein complex whose function is to add telomeric repeats to chromosomal ends. Telomerase consists of two essential components, telomerase RNA template (hTR) and catalytic subunit (hTERT). hTERT is expressed only in cells and tissues positive for telomerase activity, i.e., tumor and fetal cells. In this report, the possibility of utilization of the hTERT promoter in targeted cancer gene therapy was tested. The hTERT promoter was cloned in the replacement of the CMV promoter, and the HSV-TK gene was subcloned to be controlled by the hTERT gene promoter in the adenovirus shuttle plasmid. Then, the recombinant adenovirus Ad-hT-TK was constructed and was infected into normal and human gynecological cancer cell lines. The selective tumor specific cell death by Ad-hT-TK was identified through these experiments, showing that Ad-hT-TK could be used for targeted cancer gene therapy.

• 대한두경부종양학회지
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• 제18권1호
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• pp.18-22
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• 2002

Background and Objectives: The expression of telomerase, a ribonucleoprotein complex, has been detected in tissues from many human cancers, but not in the majority of normal tissues except germ cell. It is believed that the activation of telomerase is linked to celluar immortality and may playa role in tumorigenesis. Human telomerase reverse transcriptase (hTERT) has been identified as a putative catalytic subunit of human telomerase and its expression is closely correlated with telomease activity. We studied the expression of hTERT in head and neck squamous cell carcinoma (HNSCC) and resection margin by immunohistochemistry for hTERT and evaluate the correlation between hTERT expression and clinical data in HNSCC. Materials and Methods: We performed a immunohistochemistry in 17 cases of HNSCC and 10 cases of resection margins, histologically normal. The correlations between the hTERT expression and the clinical data in HNSCC were analyzed. Result: hTERT immunoreactivities were detected in 14 of 17 (82.4%) HNSCC, 1 of 10 (10%) resection margin. No correlation was observed between clinical data and hTERT expression in HNSCC. Conclusion: hTERT is activated in HNSCC and its expression is independent from clinical data of patients.

• BMB Reports
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• 제47권1호
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• pp.8-14
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• 2014

Telomerase plays a pivotal role in the pathology of aging and cancer by maintaining genome integrity, controlling cell proliferation, and regulating tissue homeostasis. Telomerase is essentially composed of an RNA component, Telomerase RNA or TERC, which serves as a template for telomeric DNA synthesis, and a catalytic subunit, telomerase reverse transcriptase (TERT). The canonical function of TERT is the synthesis of telomeric DNA repeats, and the maintenance of telomere length. However, accumulating evidence indicates that TERT may also have some fundamental functions that are independent of its enzymatic activity. Among these telomere-independent activities of hTERT, the role of hTERT in gene transcription has been investigated in detail. Transcriptional regulation is a fundamental process in biological systems. Several studies have shown a direct involvement of hTERT in gene transcription. This mini-review will focus on the role of hTERT in gene transcription regulation, and discuss its possible mechanisms.

• 대한화학회지
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• 제12권4호
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• pp.177-183
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• 1968

親核性 添加反應性에 있어서의 mucleophile의 反應性을 정량적으로 연구하고자 前報에 이어 여러 pH에서 3,4-methylenedioxy-$\beta$-nitrostyrene에 n-propyl- 과 tert-butylmercaptan을 첨가시켜 그의 添加反應速度常數를 측정한 결과 n-propylmercaptide ion과 tert-butylmercaptide ion에 대해 각각 $1.26{\times}10^8$과 $3.98{\times}10^6\;M^{-2},\;sec^{-1}$를 얻었으며, 또 n-propyl 및 tert-butylmercaptan 분자의 添加反應速度常數로서 $7.07{\times}10^{-3}$과 $1.5{\times}10^3\;M^{-1},\;sec^{-1}$을 각각 얻었다. 한편 염기성 뿐만 아니라 산성용매 속에서도 그의 應速 메카니즘을 잘 설명할 수 있는 全體應速度式을 구하였다.

• 한국결정학회지
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• 제6권1호
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• pp.27-35
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• 1995

1-tert-butoxycarbonyl-4-[N-(tert-butoxycarbonyl)-N-(ethoxycarbonylmethyl)amino]-3-phenylsulfonylpyrrolidind [C24H36O8N2S;이하 BEP]의 분자 및 결정구조를 X-선 회절법으로 연구하였다. 이 결정의 분자는 C24H36O8N2S, 삼사정계이고 공간군은 P1이다. 단위세포 길이는 a=11.363(8)Å, b=11.589(6)Å, c=11.013(10)Å,α=95.32(6)°,β=98.64(7)°,γ=79.57(5)°,V=1406.8(18)Å3, t=293K, Z=2이다. 구조해석에 사용한 X-선은 CuKα선(λ=1.5418Å)을 사용하였다. 분자구조는 직접법으로 풀었으며 최소자승법으로 정밀화하였다. 최종 신뢰도 R값은 F≥4 σ(F)인 3621개의 회절반점에 대하여 R=9.78% 이었다.

• Asian Pacific Journal of Cancer Prevention
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• 제14권11호
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• pp.6945-6948
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• 2013

Background: Diosgenin, a steroidal saponin from a therapeutic herb, fenugreek (Trigonellafoenum-graceum L.), has been recognized to have anticancer properties. Telomerase activity is not detected in typical healthy cells, while in cancer cell telomerase expression is reactivated, therefore providing a promising cancer therapeutic target. Materials and Methods: We studied the inhibitory effect of diosgenin on human telomerase reverse transcriptase gene (hTERT) expression which is critical for telomerase activity. MTT- assays and qRT-PCR analysis were conducted to assess cytotoxicity and hTERT gene expression inhibition effects, respectively. Results: MTT results showed that $IC_{50}$ values for 24, 48 and 72h after treatment were 47, 44 and $43{\mu}M$, respectively. Culturing cells with diosgenin treatment caused down-regulation of hTERT expression. Discussion: These results show that diosgenin inhibits telomerase activity by down-regulation of hTERT gene expression in the A549 lung cancer cell line.

• Journal of Microbiology and Biotechnology
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• 제19권9호
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• pp.1070-1076
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• 2009

Telomerase reverse transcriptase (TERT), which prolongs the replicative life span of cells, is highly upregulated in 85-90% of human cancers, whereas most normal somatic tissues in humans express limited levels of the telomerase activity. Therefore, TERT has been a potential target for anticancer therapy. Recently, we described a new approach to human cancer gene therapy, which is based on the group I intron of Tetrahymena thermophila. This ribozyme can specifically mediate RNA replacement of human TERT (hTERT) transcript with a new transcript harboring anticancer activity through a trans-splicing reaction, resulting in selective regression of hTERT-positive cancer cells. However, to validate the therapeutic potential of the ribozyme in animal models, ribozymes targeting inherent transcripts of the animal should be developed. In this study, we developed a Tetrahymena-based trans-splicing ribozyme that can specifically target and replace the mouse TERT (mTERT) RNA. This ribozyme can trigger transgene activity not only also in mTERT-expressing cells but hTERT-positive cancer cells. Importantly, the ribozyme could selectively induce activity of the suicide gene, a herpes simplex virus thymidine kinase gene, in cancer cells expressing the TERT RNA and thereby specifically hamper the survival of these cells when treated with ganciclovir. The mTERT-targeting ribozyme will be useful for evaluation of the RNA replacement approach as a cancer gene therapeutic tool in the mouse model with syngeneic tumors.

• Journal of Microbiology and Biotechnology
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• 제22권3호
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• pp.431-435
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• 2012

In this study, we describe a novel approach to achieve replicative selectivity of conditionally replicative adenovirus that is based upon trans-splicing ribozyme-mediated replacement of cancer-specific RNAs. We developed a specific ribozyme that can reprogram human telomerase reverse transcriptase (hTERT) RNA to induce adenoviral E1A gene expression selectively in cancer cells that express the RNA. Western blot analysis showed that the ribozyme highly selectively triggered E1A expression in hTERT-expressing cancer cells. RT-PCR and sequencing analysis indicated that the ribozyme-mediated E1A induction was caused via a high fidelity trans-splicing reaction with the targeted residue in the hTERT-expressing cells. Moreover, reporter activity under the control of an E1A-dependent E3 promoter was highly transactivated in hTERT-expressing cancer cells. Therefore, adenovirus containing the hTERT RNA-targeting trans-splicing ribozyme would be a promising anticancer agent through selective replication in cancer cells and thus specific destruction of the infected cells.

• Genomics & Informatics
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• 제3권4호
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• pp.172-174
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• 2005

Recent anti-cancer approaches have been based to target tumor-specifically associated and/or causative molecules such as RNAs or proteins. As this specifically targeted anti-cancer modulator, we have previously described a novel human cancer gene therapeutic agent that is Tetrahymena group I intron-based trans-splicing ribozyme which can reprogram and replace human telomerase reverse transcriptase (hTERT) RNA to selectively induce tumor-specific cytotoxicity in cancer cells expressing the target RNA. Moreover, the specific ribozyme has been shown to efficiently retard tumor tissues in xenograft mice which had been inoculated with hTERT-expressing human cancer cells. In this study, we assessed specificity of trans-splicing reaction in cells to evaluate the therapeutic feasibility of the specific ribozyme. In order to analyze the trans-spliced products by the specific ribozyme in hTERT-positive cells, RT, 5'-end RACE-PCR, and sequencing reactions of the spliced RNAs were employed. Then, whole analyzed products resulted from reactions only with the hTERT RNA. This study suggested that the developed ribozyme perform highly specific RNA replacement of the target RNA in cells, hence trans-splicing ribozyme will be one of specific agents for genetic approach to revert cancer.