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Induction of apoptotic endonuclease EndoG with DNA-damaging agents initiates alternative splicing of telomerase catalytic subunit hTERT and inhibition of telomerase activity hTERT in human CD4+ and CD8+ T-lymphocytes

Zhdanov, D.D.; Vasina, D.A.; Orlova, V.S.; Orlova, E.V.; Grishin, D.V.; Gladilina, Y.A.; Pokrovskaya, M.V.; Aleksandrova, S.S.; Sokolov, N.N.

Biomeditsinskaia Khimiia 63(4): 296-305

2017

ISSN/ISBN: 2310-6972
PMID: 28862599
Accession: 059853736
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Aktivnost' kataliticheskoĭ sub"edinitsy telomerazy hTERT (human Telomerase Reverse Transcriptase) reguliruetsia protsessom al'ternativnogo splaĭsinga ee mRNK. V nastoiashchee vremia mekhanizm splaĭsinga hTERT izuchen nedostatochno polno. Izvestno, chto v dannom protsesse prinimaet uchastie apoptoticheskaia éndonukleaza EndoG, ékspressiia kotoroĭ indutsiruetsia v otvet na povrezhdeniia DNK. Tsel'iu raboty iavliaetsia izuchenie sposobnosti povrezhdaiushchikh DNK agentov s razlichnym mekhanizmom deĭstviia vyzyvat' induktsiiu EndoG i ingibirovat' aktivnost' telomerazy v rezul'tate aktivatsii protsessa al'ternativnogo splaĭsinga hTERT v normal'nykh aktivirovannykh CD4+ i CD8+ T-limfotsitakh cheloveka. Vse issleduemye povrezhdaiushchie DNK agenty indutsirovali EndoG. Tsisplatin, khimioterapevticheskiĭ preparat, obrazuiushchiĭ sshivki DNK, vyzyval naibol'shee kolichestvo povrezhdeniĭ DNK i naibol'shuiu induktsiiu EndoG. Inkubatsiia CD4+ i CD8+ T-kletok s tsisplatinom privodila k izmeneniiu proportsii splaĭs-variantov hTERT i ingibirovaniiu aktivnosti telomerazy.

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Related References

Zhdanov, D.D.; Vasina, D.A.; Orlova, E.V.; Orlova, V.S.; Pokrovskaya, M.V.; Aleksandrova, S.S.; Sokolov, N.N. 2016: Apoptotic endonuclease EndoG regulates alternative splicing of human telomerase catalytic subunit hTERT Biomeditsinskaia Khimiia 62(5): 544-554
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