[Suppression of telomerase activity leukemic cells by mutant forms of Rhodospirillum rubrum L-asparaginase]. / Podavlenie aktivnosti telomerazy leikoznykh kletok mutantymi formami L-asparaginazy Rhodospirillum rubrum.
Biomed Khim
; 63(1): 62-74, 2017 Jan.
Article
in Ru
| MEDLINE
| ID: mdl-28251953
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 RrÐE149R, 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 RrÐ+N17, D60K, F61L and RrÐ+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.
Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Asparaginase
/
Rhodospirillum rubrum
/
Bacterial Proteins
/
Telomere
/
Point Mutation
/
Telomerase
/
Antineoplastic Agents
Language:
Ru
Journal:
Biomed Khim
Year:
2017
Type:
Article
Affiliation country:
RUSSIA