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Apoptotic endonuclease EndoG induces alternative splicing of telomerase catalytic subunit hTERT and death of tumor cells

Zhdanov, D.D.; Vasina, D.A.; Orlova, V.S.; Gotovtseva, V.Y.; Bibikova, M.V.; Pokrovsky, V.S.; Pokrovskaya, M.V.; Aleksandrova, S.S.; Sokolov, N.N.

Biomeditsinskaia Khimiia 62(3): 239-250

2016

ISSN/ISBN: 2310-6972
PMID: 27420614
DOI: 10.1134/s1990750816040090
Accession: 057220026
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Aktivnost' telomerazy reguliruetsia al'ternativnym splaĭsingom mRNK ee kataliticheskoĭ sub"edinitsy hTERT (human Telomerase Reverse Transcriptase). Uvelichenie kolichestva neaktivnoĭ splaĭs-formy hTERT ingibiruet telomeraznuiu aktivnost'. V nastoiashchee vremia mekhanizm splaĭsinga hTERT izuchen nedostatochno polno. Tsel'iu raboty bylo izuchenie vliianiia apoptoticheskoĭ éndonukleazy EndoG na al'ternativnyĭ splaĭsing hTERT i aktivnost' telomerazy. V kletkakh 12 liniĭ raka kishechnika cheloveka vyiavlena vzaimosviaz' mezhdu urovniami ékspressii EndoG i splaĭs-variantov hTERT. Sverkhékspressiia EndoG v kletkakh SaSo-2 vyzyvala snizhenie ékspressii polnorazmernogo aktivnogo varianta hTERT i uvelichenie ékspressii splaĭs-varianta. Umen'shenie kolichestva polnorazmernogo varianta hTERT privodilo k snizheniiu telomeraznoĭ aktivnosti, ukorocheniiu dliny telomer do kriticheskikh znacheniĭ, perekhodu kletok v sostoianie replikativnogo stareniia, aktivatsii apoptoticheskikh protsessov i gibeli kletok. Éti dannye ukazyvaiut na uchastie EndoG v protsesse al'ternativnogo splaĭsinga mRNK kataliticheskoĭ sub"edinitsy telomerazy i reguliatsii telomeraznoĭ aktivnosti.

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