Point mutations in human guanylate kinase account for acquired resistance to anticancer nucleotide analogue PMEG

Kód výsledku v 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>

Výsledek na webu

<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>

Jazyk výsledku

angličtina

Název v původním jazyce

Point mutations in human guanylate kinase account for acquired resistance to anticancer nucleotide analogue PMEG

Popis výsledku v původním jazyce

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.

Název v anglickém jazyce

Point mutations in human guanylate kinase account for acquired resistance to anticancer nucleotide analogue PMEG

Popis výsledku anglicky

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.

Druh

J_x - Nezařazeno - Článek v odborném periodiku (Jimp, Jsc a Jost)

CEP obor

CE - Biochemie

OECD FORD obor

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Projekt

<a href="/cs/project/1M0508" target="_blank" >1M0508: Nová antivirotika a antineoplastika</a><br>

Návaznosti

Z - Vyzkumny zamer (s odkazem do CEZ)

Rok uplatnění

2011

Kód důvěrnosti údajů

S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů

Název periodika

Biochemical Pharmacology

ISSN

0006-2952

e-ISSN

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Svazek periodika

82

Číslo periodika v rámci svazku

2

Stát vydavatele periodika

US - Spojené státy americké

Počet stran výsledku

8

Strana od-do

131-138

Kód UT WoS článku

000291760700005

EID výsledku v databázi Scopus

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