Regulation of thymidine kinase activity in the cell cycle by a labile protein

Abstract

Previous studies have shown that the onset of DNA synthesis in Balb/c 3T3 cells appears to be regulated by a labile protein. We have found that induction of thymidine kinase (TK) activity, after quiescent cells are stimulated by the addition of serum, is similarly regulated by a labile protein. Eight hours after serum stimulation, a 6‐h pulse of cycloheximide (CHM) caused an excess delay of 2h in TK induction. A similar delay also was found in the induction of thymidylate synthase (TS). In contrast, the bonzo(a)pyrene transformed 3T3 cell line, BP‐A31, which had previously been shown to have to excess delay for the onset of DNA synthesis also had no excess delay for the induction of TK activity after a pulse of CHM. The indudction of TK was inhibited by actinomycin D and dicholoribofuranosylbenzimidizole (DRB) suggesting a requirement for new RNA synthesis. It did not appear to depend on DNA synthesis as it was not blocked by aphidicolin. In conclusion, the induction of TK activity appears to be regulated by the same labile cellular signal as the onset of DNA synthesis, and to depend on an increase in the level of TK mRNA in late G₁ or early S phase.