Post-transcriptional repression of thymidine kinase expression during cell cycle and growth stimulation.
In vertebrates, endogenous thymidine kinase (TK) gene expression is strictly growth-dependent. Here we report that in continuously cycling Ltk-mouse fibroblasts, stably transfected with a vector expressing human TK cDNA from a constitutive promoter, enzyme activity rises 8-fold at the G1/S phase transition and declines again in G2. The mechanism did not involve changes in protein stability. When hTK was put under the control of a hormone-inducible promoter, production of high mRNA levels following addition of dexamethasone did not result in any enzyme activity in resting NIH-3T3tk- cells. After growth stimulation with serum, TK activity rose together with the onset of DNA synthesis only in the simultaneous presence of the hormone.
Mikulits
W
W
Institute of Molecular Biology, Vienna Biocenter, Austria.
Müllner
E W
EW
D016475:3T3 Cells; D000818:Animals; D002453:Cell Cycle / Q000187:drug effects / Q000502:physiology*; D002455:Cell Division / Q000187:drug effects / Q000502:physiology*; D003513:Cycloheximide / Q000494:pharmacology; D003907:Dexamethasone / Q000494:pharmacology; D004794:Enzyme Repression; D016193:G1 Phase; D015870:Gene Expression; D006801:Humans; D007700:Kinetics; D051379:Mice; D011401:Promoter Regions, Genetic; D014176:Protein Biosynthesis / Q000187:drug effects; D012333:RNA, Messenger / Q000096:biosynthesis / Q000378:metabolism*; D016192:Resting Phase, Cell Cycle; D016196:S Phase; D013937:Thymidine Kinase / Q000096:biosynthesis* / Q000378:metabolism; D014162:Transfection; D014714:Vertebrates
D012333:RNA, Messenger; D003907:Dexamethasone; D003513:Cycloheximide; D013937:Thymidine Kinase