THYMIDINE INHIBITS THE GROWTH-ARREST-SPECIFIC DEGRADATION OF THYMIDINE KINASE PROTEIN IN TRANSFECTED L-FIBROBLAST

The expression of murine thymidine kinase (TK) is strictly dependent o n the growth state of the cell. Expressing epitope-tagged TK in LTK(-) cells, we have previously shown that low TK enzyme levels in G(0) cel ls are in part due to a dramatic decrease in TK protein stability. Her e we report that thymidine, one of the substrates of TK, is able to co unteract the growth-arrest-specific decrease of TK expression. While T K mRNA levels and TK translation rate are almost unaffected by thymidi ne, 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, al so has the capacity to increase TK protein levels in G(0) cells, indic ating that the substrate itself exerts the stabilising effect on the T K protein. (C) 1997 Academic Press Limited