scholarly journals Telomerase activity is restored in human cells by ectopic expression of hTERT (hEST2), the catalytic subunit of telomerase

Oncogene ◽  
1998 ◽  
Vol 16 (9) ◽  
pp. 1217-1222 ◽  
Author(s):  
Christopher M Counter ◽  
Matthew Meyerson ◽  
Elinor Ng Eaton ◽  
Leif W Ellisen ◽  
Stephanie Dickinson Caddle ◽  
...  
Keyword(s):  
Ectopic Expression ◽  
Telomerase Activity ◽  
Human Cells ◽  
Catalytic Subunit

scholarly journals Apoptotic endonuclease EndoG regulates alternative splicing of human telomerase catalytic subunit hTERT

2016 ◽  
Vol 62 (5) ◽  
pp. 544-554 ◽  
Author(s):  
D.D. Zhdanov ◽  
D.A. Vasina ◽  
E.V. Orlova ◽  
V.S. Orlova ◽  
M.V. Pokrovskaya ◽  
...  
Keyword(s):  
Alternative Splicing ◽  
Telomerase Activity ◽  
Catalytic Subunit ◽  
Over Expression ◽  
Htert Gene ◽  
Template Strand ◽  
Non Coding Rna ◽  
Dna Strand ◽  
Human Telomerase ◽  
Long Non Coding Rna

Human telomerase catalytic subunit hTERT is subjected to alternative splicing results in loss of its function and leads to decrease of telomerase activity. However, very little is known about the mechanism of hTERT pre-mRNA alternative splicing. Apoptotic endonuclease EndoG is known to participate this process. The aim of this study was to determine the role of EndoG in regulation of hTERT alternative splicing. Increased expression of b-deletion splice variant was determined during EndoG over-expression in CaCo-2 cell line, after EndoG treatment of cell cytoplasm and nuclei and after nuclei incubation with EndoG digested cell RNA. hTERT alternative splicing was induced by 47-mer RNA oligonucleotide in naked nuclei and in cells after transfection. Identified long non-coding RNA, that is the precursor of 47-mer RNA oligonucleotide. Its size is 1754 nucleotides. Based on the results the following mechanism was proposed. hTERT pre-mRNA is transcribed from coding DNA strand while long non-coding RNA is transcribed from template strand of hTERT gene. EndoG digests long non-coding RNA and produces 47-mer RNA oligonucleotide complementary to hTERT pre-mRNA exon 8 and intron 8 junction place. Interaction of 47-mer RNA oligonucleotide and hTERT pre-mRNA causes alternative splicing.

scholarly journals Yil102c-A is a Functional Homologue of the DPMII Subunit of Dolichyl Phosphate Mannose Synthase in Saccharomyces cerevisiae

2020 ◽  
Vol 21 (23) ◽  
pp. 8938
Author(s):  
Sebastian Piłsyk ◽  
Urszula Perlinska-Lenart ◽  
Anna Janik ◽  
Elżbieta Gryz ◽  
Marta Ajchler-Adamska ◽  
...  
Keyword(s):  
Saccharomyces Cerevisiae ◽  
Functional Analysis ◽  
Trichoderma Reesei ◽  
Transmembrane Domain ◽  
Human Cells ◽  
Catalytic Subunit ◽  
Yeast Saccharomyces Cerevisiae ◽  
Dolichyl Phosphate ◽  
Functional Homolog ◽  
Wide Range

In a wide range of organisms, dolichyl phosphate mannose (DPM) synthase is a complex of tree proteins Dpm1, Dpm2, and Dpm3. However, in the yeast Saccharomyces cerevisiae, it is believed to be a single Dpm1 protein. The function of Dpm3 is performed in S. cerevisiae by the C-terminal transmembrane domain of the catalytic subunit Dpm1. Until present, the regulatory Dpm2 protein has not been found in S. cerevisiae. In this study, we show that, in fact, the Yil102c-A protein interacts directly with Dpm1 in S. cerevisiae and influences its DPM synthase activity. Deletion of the YIL102c-A gene is lethal, and this phenotype is reversed by the dpm2 gene from Trichoderma reesei. Functional analysis of Yil102c-A revealed that it also interacts with glucosylphosphatidylinositol-N-acetylglucosaminyl transferase (GPI-GnT), similar to DPM2 in human cells. Taken together, these results show that Yil102c-A is a functional homolog of DPMII from T. reesei and DPM2 from humans.

scholarly journals The two cytochrome c species, DC3 and DC4, are not required for caspase activation and apoptosis in Drosophila cells

2004 ◽  
Vol 167 (3) ◽  
pp. 405-410 ◽  
Author(s):  
Loretta Dorstyn ◽  
Kathryn Mills ◽  
Yuri Lazebnik ◽  
Sharad Kumar
Keyword(s):  
Cytochrome C ◽  
Ectopic Expression ◽  
Human Cells ◽  
Loss Of Function ◽  
Caspase Activation ◽  
Drosophila Cell ◽  
Drosophila Development ◽  
Cell Lysates ◽  
C Proteins ◽  
Drosophila Cells

In Drosophila, activation of the apical caspase DRONC requires the apoptotic protease-activating factor homologue, DARK. However, unlike caspase activation in mammals, DRONC activation is not accompanied by the release of cytochrome c from mitochondria. Drosophila encodes two cytochrome c proteins, Cytc-p (DC4) the predominantly expressed species, and Cytc-d (DC3), which is implicated in caspase activation during spermatogenesis. Here, we report that silencing expression of either or both DC3 and DC4 had no effect on apoptosis or activation of DRONC and DRICE in Drosophila cells. We find that loss of function mutations in dc3 and dc4, do not affect caspase activation during Drosophila development and that ectopic expression of DC3 or DC4 in Drosophila cells does not induce caspase activation. In cell-free studies, recombinant DC3 or DC4 failed to activate caspases in Drosophila cell lysates, but remarkably induced caspase activation in extracts from human cells. Overall, our results argue that DARK-mediated DRONC activation occurs independently of cytochrome c.

Inhibition of telomerase activity by splice-switching oligonucleotides targeting the mRNA of the telomerase catalytic subunit affects proliferation of human CD4+ T lymphocytes

2019 ◽  
Vol 509 (3) ◽  
pp. 790-796 ◽  
Author(s):  
Dmitry D. Zhdanov ◽  
Anna A. Plyasova ◽  
Yulia A. Gladilina ◽  
Vadim S. Pokrovsky ◽  
Dmitry V. Grishin ◽  
...  
Keyword(s):  
T Lymphocytes ◽  
Telomerase Activity ◽  
Catalytic Subunit

scholarly journals TIN2 Functions with TPP1/POT1 To Stimulate Telomerase Processivity

2019 ◽  
Vol 39 (21) ◽  
Author(s):  
Alexandra M. Pike ◽  
Margaret A. Strong ◽  
John Paul T. Ouyang ◽  
Carol W. Greider
Keyword(s):  
Telomere Length ◽  
Telomerase Activity ◽  
Human Cells ◽  
Short Telomere ◽  
Gene Encoding ◽  
Important Regulator

ABSTRACT TIN2 is an important regulator of telomere length, and mutations in TINF2, the gene encoding TIN2, cause short-telomere syndromes. While the genetics underscore the importance of TIN2, the mechanism through which TIN2 regulates telomere length remains unclear. Here, we tested the effects of human TIN2 on telomerase activity. We identified a new isoform in human cells, TIN2M, that is expressed at levels similar to those of previously studied TIN2 isoforms. All three TIN2 isoforms localized to and maintained telomere integrity in vivo, and localization was not disrupted by telomere syndrome mutations. Using direct telomerase activity assays, we discovered that TIN2 stimulated telomerase processivity in vitro. All of the TIN2 isoforms stimulated telomerase to similar extents. Mutations in the TPP1 TEL patch abrogated this stimulation, suggesting that TIN2 functions with TPP1/POT1 to stimulate telomerase processivity. We conclude from our data and previously published work that TIN2/TPP1/POT1 is a functional shelterin subcomplex.

scholarly journals Telomere length: how the length makes a difference

2020 ◽  
Vol 47 (9) ◽  
pp. 7181-7188 ◽  
Author(s):  
M. Lulkiewicz ◽  
J. Bajsert ◽  
P. Kopczynski ◽  
W. Barczak ◽  
B. Rubis
Keyword(s):  
Telomere Length ◽  
Meta Analysis ◽  
Telomerase Activity ◽  
Human Cells ◽  
Attrition Rate ◽  
Severe Damage ◽  
Telomere Attrition ◽  
Adult Men ◽  
Cell Life ◽  
Real Value

Abstract Telomerase is perceived as an immortality enzyme that might provide longevity to cells and whole organisms. Importantly, it is generally inactive in most somatic cells of healthy, adult men. Consequently, its substrates, i.e. telomeres, get shorter in most human cells with time. Noteworthy, cell life limitation due to telomere attrition during cell divisions, may not be as bad as it looks since longer cell life means longer exposition to harmful factors. Consequently, telomere length (attrition rate) becomes a factor that is responsible for inducing the signaling that leads to the elimination of cells that lived long enough to acquire severe damage. It seems that telomere length that depends on many different factors (including telomerase activity but also genetic factors, a hormonal profile that reflects sex, etc.) might become a useful marker of aging and exposition to stress. Thus in the current paper, we review the factors that affect telomere length in human cells focusing on sex that all together with different environmental and hormonal regulations as well as parental aspect affect telomere attrition rate. We also raise some limitations in the assessment of telomere length that hinders a trustworthy meta-analysis that might lead to acknowledgment of the real value of this parameter.

scholarly journals Absence of telomerase activity and telomerase catalytic subunit mRNA in melanocyte cultures

2000 ◽  
Vol 82 (5) ◽  
pp. 1051-1057 ◽  
Author(s):  
K Dhaene ◽  
G Vancoillie ◽  
J Lambert ◽  
J M Naeyaert ◽  
E Van Marck
Keyword(s):  
Telomerase Activity ◽  
Catalytic Subunit ◽  
Subunit Mrna

scholarly journals Lack of cell cycle regulation of telomerase activity in human cells

1997 ◽  
Vol 94 (20) ◽  
pp. 10687-10692 ◽  
Author(s):  
S. E. Holt ◽  
D. L. Aisner ◽  
J. W. Shay ◽  
W. E. Wright
Keyword(s):  
Cell Cycle ◽  
Cell Cycle Regulation ◽  
Telomerase Activity ◽  
Human Cells ◽  
Cycle Regulation

scholarly journals Derepression of hTERT gene expression promotes escape from oncogene-induced cellular senescence

2016 ◽  
Vol 113 (34) ◽  
pp. E5024-E5033 ◽  
Author(s):  
Priyanka L. Patel ◽  
Anitha Suram ◽  
Neena Mirani ◽  
Oliver Bischof ◽  
Utz Herbig
Keyword(s):  
Dna Damage ◽  
Cancer Progression ◽  
Ectopic Expression ◽  
Telomerase Activity ◽  
Early Event ◽  
Telomere Dysfunction ◽  
Telomeric Dna ◽  
Human Telomerase Reverse Transcriptase ◽  
Htert Gene ◽  
In Cells

Oncogene-induced senescence (OIS) is a critical tumor-suppressing mechanism that restrains cancer progression at premalignant stages, in part by causing telomere dysfunction. Currently it is unknown whether this proliferative arrest presents a stable and therefore irreversible barrier to cancer progression. Here we demonstrate that cells frequently escape OIS induced by oncogenic H-Ras and B-Raf, after a prolonged period in the senescence arrested state. Cells that had escaped senescence displayed high oncogene expression levels, retained functional DNA damage responses, and acquired chromatin changes that promoted c-Myc–dependent expression of the human telomerase reverse transcriptase gene (hTERT). Telomerase was able to resolve existing telomeric DNA damage response foci and suppressed formation of new ones that were generated as a consequence of DNA replication stress and oncogenic signals. Inhibition of MAP kinase signaling, suppressing c-Myc expression, or inhibiting telomerase activity, caused telomere dysfunction and proliferative defects in cells that had escaped senescence, whereas ectopic expression of hTERT facilitated OIS escape. In human early neoplastic skin and breast tissue, hTERT expression was detected in cells that displayed features of senescence, suggesting that reactivation of telomerase expression in senescent cells is an early event during cancer progression in humans. Together, our data demonstrate that cells arrested in OIS retain the potential to escape senescence by mechanisms that involve derepression of hTERT expression.

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