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

被引：5

作者：

Pokrovskaya M.V. ^{[1
]}

Zhdanov D.D. ^{[1
]}

Eldarov M.A. ^{[2
]}

Aleksandrova S.S. ^{[1
]}

Veselovsky A.V. ^{[1
]}

Pokrovskiy V.S. ^{[1
,3
]}

Grishin D.V. ^{[1
]}

Gladilina J.A. ^{[1
]}

Sokolov N.N. ^{[1
]}

机构：

[1] Institute of Biomedical Chemistry, ul. Pogodinskaya 10, Moscow

[2] Research Center of Biotechnology RAS, Leninsky pr. 33, Moscow

[3] Blokhin Cancer Research Center, Kashirskoe Shosse, 24, Moscow

来源：

Biochemistry (Moscow), Supplement Series B: Biomedical Chemistry | 2017年 / 11卷 / 3期

关键词：

a site-directed mutagenesis; antineoplastic effect of L-asparaginase; hTERT subunit of telomerase; L-asparaginase Rhodospirillum rubrum; telomerase;

D O I：

10.1134/S1990750817030088

中图分类号：

学科分类号：

摘要：

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. © 2017, Pleiades Publishing, Ltd.

引用

页码：219 / 233

页数：14

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