Regulation of Telomerase Activity

Налобин, Д. С.; Galiakberova, Adelya A.; Alipkina, S. I.; Глухов, А.И.

doi:10.1134/s2079086418020068

Cited by 3 publications

(10 citation statements)

References 82 publications

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Section: Post Translational Regulation Of Tertmentioning

confidence: 99%

“…In phosphorylation, kinases such as protein phosphatase 2A (PP2A) interact with c-Abl tyrosine kinase protein, leading to a threefold reduction of telomerase activity by dephosphorylation [53,68,69]. On the contrary, protein kinase B (an AKT kinase) increases telomerase activity through TERT phosphorylation-dependent activation of the PI3K/Akt/mTOR pathway [68,69]. Similar to protein kinase C, they phosphorylate hTERT by PKC isoenzymes α, β, δ, ε, and ζ to enhance telomerase activity, which is increased along with nuclear accumulation of hTERT [61,66,[69][70][71].…”

Section: Post Translational Regulation Of Tertmentioning

confidence: 99%

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Mechanism of Human Telomerase Reverse Transcriptase (hTERT) Regulation and Clinical Impacts in Leukemia

Yik

Aziz

Rajasegaran

et al. 2021

Genes

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The proliferative capacity and continuous survival of cells are highly dependent on telomerase expression and the maintenance of telomere length. For this reason, elevated expression of telomerase has been identified in virtually all cancers, including leukemias; however, it should be noted that expression of telomerase is sometimes observed later in malignant development. This time point of activation is highly dependent on the type of leukemia and its causative factors. Many recent studies in this field have contributed to the elucidation of the mechanisms by which the various forms of leukemias increase telomerase activity. These include the dysregulation of telomerase reverse transcriptase (TERT) at various levels which include transcriptional, post-transcriptional, and post-translational stages. The pathways and biological molecules involved in these processes are also being deciphered with the advent of enabling technologies such as next-generation sequencing (NGS), ribonucleic acid sequencing (RNA-Seq), liquid chromatography-mass spectrometry (LCMS/MS), and many others. It has also been established that TERT possess diagnostic value as most adult cells do not express high levels of telomerase. Indeed, studies have shown that prognosis is not favorable in patients who have leukemias expressing high levels of telomerase. Recent research has indicated that targeting of this gene is able to control the survival of malignant cells and therefore offers a potential treatment for TERT-dependent leukemias. Here we review the mechanisms of hTERT regulation and deliberate their association in malignant states of leukemic cells. Further, we also cover the clinical implications of this gene including its use in diagnostic, prognostic, and therapeutic discoveries.

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Section: Post Translational Regulation Of Tertmentioning

confidence: 99%

Section: Post Translational Regulation Of Tertmentioning

confidence: 99%

Mechanism of Human Telomerase Reverse Transcriptase (hTERT) Regulation and Clinical Impacts in Leukemia

Yik

Aziz

Rajasegaran

et al. 2021

Genes

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Section: Telomeres and Telomere Complexmentioning

confidence: 99%

“…Ten years after the discovery of the Hayflick limit, Olovnikov hypothesized that DNA polymerase cannot copy a small region at the end of chromosome (telomere), which leads to terminal under-replication of DNA [2] (Figure 1). Scientists postulated that telomeres undergo shortening with each cell division and assumed that this phenomenon was associated with the cell division limit.…”

Section: Telomeres and Telomere Complexmentioning

confidence: 99%

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Telomeres and Telomerase in Heart Ontogenesis, Aging and Regeneration

Налобин

Alipkina

Gaidamaka

et al. 2020

Cells

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The main purpose of the review article is to assess the contributions of telomere length and telomerase activity to the cardiac function at different stages of development and clarify their role in cardiac disorders. It has been shown that the telomerase complex and telomeres are of great importance in many periods of ontogenesis due to the regulation of the proliferative capacity of heart cells. The review article also discusses the problems of heart regeneration and the identification of possible causes of dysfunction of telomeres and telomerase.

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Phenotypical and Functional Characteristics of Human Regulatory T Cells during Ex Vivo Maturation from CD4+ T Lymphocytes

et al. 2021

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Regulatory T cells (Tregs) participate in the negative regulation of inflammatory reactions by suppressing effector cells. In a number of autoimmune disorders, the suppressive function and/or the number of Tregs is compromised. The lack of active functioning Tregs can be restored with adoptive transfer of expanded ex vivo autologous Tregs. In our study, we traced the differentiation and maturation of Tregs CD4+CD25+FoxP3+CD127low over 7 days of cultivation from initial CD4+ T cells under ex vivo conditions. The resulting ex vivo expanded cell population (eTregs) demonstrated the immune profile of Tregs with an increased capacity to suppress the proliferation of target effector cells. The expression of the FoxP3 gene was upregulated within the time of expansion and was associated with gradual demethylation in the promotor region of the T cell-specific demethylation region. Real-time RT-PCR analysis revealed changes in the expression profile of genes involved in cell cycle regulation. In addition to FOXP3, the cells displayed elevated mRNA levels of Ikaros zinc finger transcription factors and the main telomerase catalytic subunit hTERT. Alternative splicing of FoxP3, hTERT and IKZF family members was demonstrated to be involved in eTreg maturation. Our data indicate that expanded ex vivo eTregs develop a Treg-specific phenotype and functional suppressive activity. We suggest that eTregs are not just expanded but transformed cells with enhanced capacities of immune suppression. Our findings may influence further development of cell immunosuppressive therapy based on regulatory T cells.

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Regulation of Telomerase Activity

Cited by 3 publications

References 82 publications

Mechanism of Human Telomerase Reverse Transcriptase (hTERT) Regulation and Clinical Impacts in Leukemia

Mechanism of Human Telomerase Reverse Transcriptase (hTERT) Regulation and Clinical Impacts in Leukemia

Telomeres and Telomerase in Heart Ontogenesis, Aging and Regeneration

Phenotypical and Functional Characteristics of Human Regulatory T Cells during Ex Vivo Maturation from CD4+ T Lymphocytes

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