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Biochemistry (Moscow)

, Volume 82, Issue 1, pp 24–37 | Cite as

Apoptotic endonuclease EndoG inhibits telomerase activity and induces malignant transformation of human CD4+ T cells

  • D. A. Vasina
  • D. D. ZhdanovEmail author
  • E. V. Orlova
  • V. S. Orlova
  • M. V. Pokrovskaya
  • S. S. Aleksandrova
  • N. N. Sokolov
Article

Abstract

Telomerase activity is regulated by an alternative splicing of mRNA of the telomerase catalytic subunit hTERT (human telomerase reverse transcriptase). Increased expression of the inactive spliced hTERT results in inhibition of telomerase activity. Little is known about the mechanism of hTERT mRNA alternative splicing. This study was aimed at determining the effect of an apoptotic endonuclease G (EndoG) on alternative splicing of hTERT and telomerase activity in CD4+ human T lymphocytes. Overexpression of EndoG in CD4+ T cells downregulated the expression of the active fulllength hTERT variant and upregulated the inactive alternatively spliced variant. Reduction of full-length hTERT levels caused downregulation of the telomerase activity, critical telomere shortening during cell division that converted cells into the replicative senescence state, activation of apoptosis, and finally cell death. Some cells survive and undergo a malignant transformation. Transformed cells feature increased telomerase activity and proliferative potential compared to the original CD4+ T cells. These cells have phenotype of T lymphoblastic leukemia cells and can form tumors and cause death in experimental mice.

Keywords

EndoG telomerase hTERT alternative splicing malignant transformation 

Abbreviations

EndoG

endonuclease G

FITC

fluorescein isothiocyanate

GAPDH

glyceraldehyde-3-phosphatedehydrogenase

GFP

green fluorescent protein

hTERT

human telomerase reverse transcriptase

MFI

mean fluorescence intensity

TRAP

telomeric repeats amplification protocol

ß-Gal

ß-galactosidase

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Copyright information

© Pleiades Publishing, Ltd. 2017

Authors and Affiliations

  • D. A. Vasina
    • 1
  • D. D. Zhdanov
    • 1
    • 2
    Email author
  • E. V. Orlova
    • 3
  • V. S. Orlova
    • 1
  • M. V. Pokrovskaya
    • 2
  • S. S. Aleksandrova
    • 2
  • N. N. Sokolov
    • 2
  1. 1.Ecological FacultyPeoples’ Friendship University of RussiaMoscowRussia
  2. 2.Institute of Biomedical ChemistryMoscowRussia
  3. 3.Institute of Theoretical and Experimental BiophysicsPushchino, Moscow RegionRussia

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