Effect of deoxynucleoside analogs on the activity of deoxycytidine kinase

T. Spasokoukotskaia, M. Sasvari-Szekely, F. Albertioni, S. Eriksson, M. Staub

Research output: Contribution to journalArticle

Abstract

Deoxycytidine kinase (dCK) was shown to be activated during short time treatment of human lymphocytes by 2-chlorodeoxyadenosine (CdA), under the conditions when the DNA synthesis is inhibited. G-phase cells showed more profound stimulation of dCK activity than S-phase cells. CdA treatment increased the activity of dCK 4 times in peripheral blood lymphocytes, and 2 times in promyelocytic cell line HL60. However, no significant stimulation was detected either in CCRF-CEM T-lymphoblastoid or in K562 myeloid cell lines. 2Cl-2′deoxy-2′F-adenine arabinoside, 2F-adenine arabmoside, dA with deoxycoformycine (dCF) and cytosine arabinoside had a similar effect as CdA, although higher concentrations were needed for maximal activation. In contrast. dA without dCF and 2C1-A had no substantial effect at any concentration used, while treatment by dC caused slight inhibition of dCK and prevented its activation by CdA. No changes in activities of dTKs, dGK and catabolic pathways were detected. Our results show, that (i) nucleoside analogues should be activated to exert their stimulatory effect on dCK, (ii) as the increase of dCK activity was shown in crude cell extracts, without any increase in the amount of dCK mRNA and protein, a secondary modification of the protein structure was considered.

Original languageEnglish
Pages (from-to)A1113
JournalFASEB Journal
Volume11
Issue number9
Publication statusPublished - Dec 1 1997

ASJC Scopus subject areas

  • Biotechnology
  • Biochemistry
  • Molecular Biology
  • Genetics

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