TheImmediate-Early GeneEgr-1Regulates theActivity ofthe Thymidine Kinase Promoter attheGo-to-G1 Transition oftheCellCycle

andtranslational levels tocausea 40-to50-fold increase incytosolic enzymatic activity ascells progressfromG,toSphase. Transcriptional activation ofthe mouse TK genethrough thecell cycle isdependent upon previously characterized ciselements oftheproximal promoter, called MT1,MT2,andMT3,thatbindat.least twodifferent complexes: TKEduring thetransition ofcells fromquiescence (Go) toG1,andYilater attheGJ/S boundary. Toidentify thetranscription factors involved inthisregulation, we screened a mouse fibroblast cDNAexpression library witha labeled MT3 oligonucleotide probe andisolated a clone thatencodes Egr-1, an immediate-early transcription factor, whose expression isregulated byserum orgrowth factors during theGo-to-G1 transition whencells reenter thecell cycle. Electrophoretic mobility shift assaysdemonstrate thatEgr-1 isinvolved intheTKEcomplex thatbinds totheMT3 element andthatexpression ofEgr-1induces transcription ofa mouse TK-chloramphenicol acetyltransferase reporter intransient transfections. Theseresults suggest a roleforEgr-1inregulating expression oftheTK gene attheGo-to-G, transition. Thymidine kinase (TK)isacytosolic enzymethat catalyzes thephosphorylation ofthymidine toformdTMP,aprecursor ofDNA.Likeother genesencoding enzymes thatparticipate inthebiosynthesis ofDNA,theTK geneisregulated at transcriptional, posttranscriptional, andtranslational levels to