Apoptotic endonuclease EndoG inhibits telomerase activity and induces malignant transformation of human CD4+ T cells
- 作者: Vasina D.1, Zhdanov D.1,2, Orlova E.3, Orlova V.1, Pokrovskaya M.2, Aleksandrova S.2, Sokolov N.2
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隶属关系:
- Ecological Faculty
- Institute of Biomedical Chemistry
- Institute of Theoretical and Experimental Biophysics
- 期: 卷 82, 编号 1 (2017)
- 页面: 24-37
- 栏目: Article
- URL: https://journals.rcsi.science/0006-2979/article/view/151213
- DOI: https://doi.org/10.1134/S0006297917010035
- ID: 151213
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详细
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.
作者简介
D. Vasina
Ecological Faculty
Email: zhdanovdd@mail.ru
俄罗斯联邦, Moscow, 117198
D. Zhdanov
Ecological Faculty; Institute of Biomedical Chemistry
编辑信件的主要联系方式.
Email: zhdanovdd@mail.ru
俄罗斯联邦, Moscow, 117198; Moscow, 119121
E. Orlova
Institute of Theoretical and Experimental Biophysics
Email: zhdanovdd@mail.ru
俄罗斯联邦, Pushchino, Moscow Region, 142290
V. Orlova
Ecological Faculty
Email: zhdanovdd@mail.ru
俄罗斯联邦, Moscow, 117198
M. Pokrovskaya
Institute of Biomedical Chemistry
Email: zhdanovdd@mail.ru
俄罗斯联邦, Moscow, 119121
S. Aleksandrova
Institute of Biomedical Chemistry
Email: zhdanovdd@mail.ru
俄罗斯联邦, Moscow, 119121
N. Sokolov
Institute of Biomedical Chemistry
Email: zhdanovdd@mail.ru
俄罗斯联邦, Moscow, 119121