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Suppression of telomerase activity in leukemic cells by mutant forms of Rhodospirillum rubrum L-asparaginase

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Abstract

Active and stable mutant forms of short chain cytoplasmic L-asparaginase type I of Rhodospirillum rubrum (RrA) (RrA+N17, D60K, F61L, RrA+N17, A64V, E67K, RrA+N17, E149R, V150P, RrAE149R, V150P and RrAE149R, V150P, F151T) have been obtained by the method of site-directed mutagenesis. The variants RrAE149R, V150P, F151T and RrА+N17, E149R, V150P could decrease reduce expression of the hTERT telomerase subunit and, therefore, activity of telomeres in Jurkat cells, but not in cellular lysates. At the same time, L-asparaginasеs of Escherichia coli, Erwinia carotovora, and Wolinella succinogenes, mutant forms RrА+N17, D60K, F61L and RrА+N17, A64V, E67K did not suppress telomerase activity. It is suggested that some regions in the RrA structure (amino acids residues 146–164, 1–17, 60–67) are responsible for suppression of telomerase activity. The results obtained show that antineoplastic activity of some RrA variants is associated both with reduction of concentration of free L-asparagine, and with decreased expression of the hTERT telomerase subunit; this opens new prospects for antineoplastic therapy.

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Authors and Affiliations

  1. Institute of Biomedical Chemistry, ul. Pogodinskaya 10, Moscow, 119121, Russia

    M. V. Pokrovskaya, D. D. Zhdanov, S. S. Aleksandrova, A. V. Veselovsky, V. S. Pokrovskiy, D. V. Grishin, Ju. A. Gladilina & N. N. Sokolov

  2. Research Center of Biotechnology RAS, Leninsky pr. 33, Moscow, 119071, Russia

    M. A. Eldarov

  3. Blokhin Cancer Research Center, Kashirskoe Shosse, 24, Moscow, 115478, Russian Federation

    V. S. Pokrovskiy

Authors
  1. M. V. Pokrovskaya
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  2. D. D. Zhdanov
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  3. M. A. Eldarov
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  4. S. S. Aleksandrova
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  5. A. V. Veselovsky
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  6. V. S. Pokrovskiy
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  7. D. V. Grishin
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  8. Ju. A. Gladilina
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  9. N. N. Sokolov
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Correspondence to M. V. Pokrovskaya.

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Original Russian Text © M.V. Pokrovskaya, D.D. Zhdanov, M.A. Eldarov, S.S. Aleksandrova, A.V. Veselovsky, V.S. Pokrovskiy, D.V. Grishin, Ju.A. Gladilina, N.N. Sokolov, 2017, published in Biomeditsinskaya Khimiya.

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Pokrovskaya, M.V., Zhdanov, D.D., Eldarov, M.A. et al. Suppression of telomerase activity in leukemic cells by mutant forms of Rhodospirillum rubrum L-asparaginase. Biochem. Moscow Suppl. Ser. B 11, 219–233 (2017). https://doi.org/10.1134/S1990750817030088

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