Overexpression of a Heterologous Thymidine Kinase Delays Apoptosis Induced by Factor Deprivation and Inhibitors of Deoxynucleotide Metabolism*

Perturbing deoxyribonucleoside triphosphate (dNTP) metabolism with inhibitors of the de novo synthesis of dNTP causes apoptosis in the interleukin-3 (IL-3)-dependent pre-B cell line BAF3. Under these conditions apoptosis is prevented when deoxyribonucleosides for dNTP synthesis are supplied in the culture medium. On the other hand, removal of IL-3 from cultures of BAF3 cells resulted in down-regulation of thymidine kinase activity, rapid imbalance in dNTP levels, and apoptosis. In this study we show that overexpression of a heterologous thymidine kinase, herpes simplex virus thymidine kinase (TK), in BAF3 cells protects these cells from apoptosis induced by either inhibitors of dNTP synthesis or IL-3 deprivation. This protection against apoptosis is abrogated by 9-(4-hydroxybutyl)-N 2-phenylguanine, a specific inhibitor of herpes simplex virus-1 TK. These results suggest that deoxyribonucleoside kinases, particularly TK, may be important in the regulation of apoptosis in hemopoietic cells.

• Publication year

  1997

• Venue

  Journal of Biological Chemistry

• Publication date

  1997-04-18

• Fields of study

  Biology, Medicine

• Identifiers
  DOI 10.1074/JBC.272.16.10624PMID 9099710
• External record

  Open on Semantic Scholar

• Source metadata

  Semantic Scholar, PubMed

• No claims are published for this paper.

• No concepts are published for this paper.

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