title: [Suppression of telomerase activity leukemic cells by mutant forms of Rhodospirillum rubrum L-asparaginase].
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-asparaginases 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.
authors.affiliation: Institute of Biomedical Chemistry, Moscow, Russia.
authors.forename: M V
authors.initials: MV
authors.lastname: Pokrovskaya
authors.affiliation: Institute of Biomedical Chemistry, Moscow, Russia.
authors.forename: D D
authors.initials: DD
authors.lastname: Zhdanov
authors.affiliation: Research Center of Biotechnology RAS, Moscow, Russia.
authors.forename: M A
authors.initials: MA
authors.lastname: Eldarov
authors.affiliation: Institute of Biomedical Chemistry, Moscow, Russia.
authors.forename: S S
authors.initials: SS
authors.lastname: Aleksandrova
authors.affiliation: Institute of Biomedical Chemistry, Moscow, Russia.
authors.forename: A V
authors.initials: AV
authors.lastname: Veselovskiy
authors.affiliation: N.N. Blokhin Russian Cancer Research Center, Moscow, Russia.
authors.forename: V S
authors.initials: VS
authors.lastname: Pokrovskiy
authors.affiliation: Institute of Biomedical Chemistry, Moscow, Russia.
authors.forename: D V
authors.initials: DV
authors.lastname: Grishin
authors.affiliation: Institute of Biomedical Chemistry, Moscow, Russia.
authors.forename: Ju A
authors.initials: JA
authors.lastname: Gladilina
authors.affiliation: Institute of Biomedical Chemistry, Moscow, Russia.
authors.forename: N N
authors.initials: NN
authors.lastname: Sokolov
mesh_terms: D000595:Amino Acid Sequence; D000970:Antineoplastic Agents / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology*; D001215:Asparaginase / Q000737:chemistry / Q000235:genetics / Q000378:metabolism / Q000494:pharmacology*; D001426:Bacterial Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism / Q000494:pharmacology*; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D004926:Escherichia coli / Q000737:chemistry / Q000201:enzymology / Q000235:genetics; D015870:Gene Expression; D018922:HL-60 Cells; D006801:Humans; D019169:Jurkat Cells; D008958:Models, Molecular; D016297:Mutagenesis, Site-Directed; D016973:Pectobacterium carotovorum / Q000737:chemistry / Q000201:enzymology / Q000235:genetics; D010957:Plasmids / Q000737:chemistry / Q000378:metabolism; D017354:Point Mutation; D017433:Protein Structure, Secondary; D012247:Rhodospirillum rubrum / Q000737:chemistry / Q000201:enzymology* / Q000235:genetics; D013045:Species Specificity; D013329:Structure-Activity Relationship; D019098:Telomerase / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism; D016615:Telomere / Q000737:chemistry / Q000187:drug effects*; D016968:Wolinella / Q000737:chemistry / Q000201:enzymology / Q000235:genetics
chemical_list: D000970:Antineoplastic Agents; D001426:Bacterial Proteins; C509186:TERT protein, human; D019098:Telomerase; D001215:Asparaginase
keywords: L-asparaginase Rhodospirillum rubrum; a site-directed mutagenesis; antineoplastic effect of L-asparaginase; hTERT subunit of telomerase; telomerase