Point mutations in human guanylate kinase account for acquired resistance to anticancer nucleotide analogue PMEG
The result's identifiers
Result code in IS VaVaI
<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F61388963%3A_____%2F11%3A00360711" target="_blank" >RIV/61388963:_____/11:00360711 - isvavai.cz</a>
Result on the web
<a href="http://dx.doi.org/10.1016/j.bcp.2011.04.002" target="_blank" >http://dx.doi.org/10.1016/j.bcp.2011.04.002</a>
DOI - Digital Object Identifier
<a href="http://dx.doi.org/10.1016/j.bcp.2011.04.002" target="_blank" >10.1016/j.bcp.2011.04.002</a>
Alternative languages
Result language
angličtina
Original language name
Point mutations in human guanylate kinase account for acquired resistance to anticancer nucleotide analogue PMEG
Original language description
The ability of a nucleotide analogue PMEG to induce resistance and the mechanisms involved were adressed. CCRF-CEM cells resistant to either PMEG or its congener PMEDAP were assayed for the expression of membrane transporters, PMEG and PMEDAP uptake andmetabolism. PMEG phosphorylation to PMEG mono- and diphosphate was completely impaired in resistant cells. Guanylate kinase (GUK) obtained from PMEG-resistant cells revealed two point mutations S(35)N V(168)F that significantly suppressed its catalytic activity. Transfection with wtGUK led to the recovery of phosphorylating activity and sensitivity towards PMEG cytotoxicity. Primary sequence of adenylate kinase (AK) from PMEDAP resistant cells was unaffected. Resistance induced by PMEDAP is thus conferred by other mechanisms. No differences in PMEG uptake have been found between sensitive and resistant cells. GUK was identified as the sole molecular target for the development of resistance to PMEG.
Czech name
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Czech description
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Classification
Type
J<sub>x</sub> - Unclassified - Peer-reviewed scientific article (Jimp, Jsc and Jost)
CEP classification
CE - Biochemistry
OECD FORD branch
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Result continuities
Project
<a href="/en/project/1M0508" target="_blank" >1M0508: New Antivirals and Antineoplastics</a><br>
Continuities
Z - Vyzkumny zamer (s odkazem do CEZ)
Others
Publication year
2011
Confidentiality
S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů
Data specific for result type
Name of the periodical
Biochemical Pharmacology
ISSN
0006-2952
e-ISSN
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Volume of the periodical
82
Issue of the periodical within the volume
2
Country of publishing house
US - UNITED STATES
Number of pages
8
Pages from-to
131-138
UT code for WoS article
000291760700005
EID of the result in the Scopus database
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