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


1. Institute of Biomedical Chemistry, Moscow, Russia
2. Research Center of Biotechnology RAS, Moscow, Russia
3. N.N. Blokhin Russian Cancer Research Center, Moscow, Russia
Type: Experimental study
DOI: 10.18097/PBMC20176301062      PubMed Id: 28251953
Year: 2017 vol: 63  issue:1  pages: 62-74
Abstract: The 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 were obtained by the method of site-directed mutagenesis. It is established that variants RrA-N17, E149R, V150P, F151T and RrАE149R, V150P are capable to reduce an expression hTERT subunit of telomerase and, hence, activity of telomeres in Jurkat cells, but not in cellular lysates. During too time, L-asparaginasеs of Escherichia coli, Erwinia carotovora and Wolinella succinogenes, mutant forms RrА+N17, D60K, F61L and RrА+N17, A64V, E67K do not suppress of telomerase activity. The assumption of existence in structure RrA of areas (amino acids residues in the position 146-164, 1-17, 60-67) which are responsible for suppression of telomerase activity is made. The received results show that antineoplastic activity of some variants RrA is connected both with reduction of concentration of free L-asparagine, and with expression suppression of hTERT telomerase subunit, that opens new prospects for antineoplastic therapy.
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Reference: Pokrovskaya M.V., Zhdanov D.D., Eldarov M.A., Aleksandrova S.S., Veselovskiy A.V., Pokrovskiy V.S., Grishin D.V., Gladilina Ju.A., Sokolov N.N., Suppression of telomerase activity leukemic cells by mutant forms of Rhodospirillum rubrum L-asparaginase, Biomeditsinskaya khimiya, 2017, vol: 63(1), 62-74.