PMID:28320284

Citation	Vasina, DA, Zhdanov, DD, Orlova, EV, Orlova, VS, Pokrovskaya, MV, Aleksandrova, SS and Sokolov, NN (2017) Apoptotic Endonuclease EndoG Inhibits Telomerase Activity and Induces Malignant Transformation of Human CD4+ T Cells. Biochemistry Mosc. 82:24-37
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 full-length 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.
Links	PubMed Online version:10.1134/S0006297917010035
Keywords	Alternative Splicing; Animals; CD4-Positive T-Lymphocytes/enzymology; CD4-Positive T-Lymphocytes/pathology; Cell Transformation, Neoplastic/genetics; Cell Transformation, Neoplastic/metabolism; Cell Transformation, Neoplastic/pathology; Endodeoxyribonucleases/biosynthesis; Endodeoxyribonucleases/genetics; Female; Gene Expression Regulation, Enzymologic; Gene Expression Regulation, Neoplastic; Heterografts; Humans; Male; Mice; Neoplasm Proteins/biosynthesis; Neoplasm Proteins/genetics; Neoplasm Transplantation; Precursor T-Cell Lymphoblastic Leukemia-Lymphoma/enzymology; Precursor T-Cell Lymphoblastic Leukemia-Lymphoma/genetics; Precursor T-Cell Lymphoblastic Leukemia-Lymphoma/pathology; Telomerase/biosynthesis; Telomerase/genetics; Telomere Homeostasis
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