Thymidine inhibits the growth-arrest-specific degradation of thymidine kinase protein in transfected L fibroblasts.

The expression of murine thymidine kinase (TK) is strictly dependent on the growth state of the cell. Expressing epitope-tagged TK in LTK cells, we have previously shown that low TK enzyme levels in G0 cells are in part due to a dramatic decrease in TK protein stability. Here we report that thymidine, one of the substrates of TK, is able to counteract the growth-arrest-specific decrease of TK expression. While TK mRNA levels and TK translation rate are almost unaffected by thymidine, the TK protein half-life rose more than sixfold after addition of the nucleoside to resting cells. The effect of thymidine is reversible and is independent of its presence during the protein synthesis of TK. Dideoxythymidine, a specific inhibitor of the TK enzyme activity, also has the capacity to increase TK protein levels in G0 cells, indicating that the substrate itself exerts the stabilising effect on the TK protein.