Different members of the jun proto-oncogene family exhibit distinct patterns of expression in response to type β transforming growth factor

Type β transforming growth factor (TGF-β) is a multifunctional regulator of cell growth and differentiation. In the BC₃H1 muscle cell line, TGF-β blocks the onset of differentiation when added to undifferentiated myoblasts and causes dedifferentiation when added to fully differentiated myocytes. The goal of the present study was to determine whether TGF-β-dependent repression of muscle-specific genes was preceded by modulation in expression of members of the jun protooncogene family, which function as growth factor-inducible transcription factors. junB mRNA was expressed at a basal level in differentiated BC₃H1 myocytes. Within 15 min following exposure of myocytes to TGF-β, junB mRNA began to accumulate; a peak of expression 20-fold above basal levels was observed after 2 h with a gradual decline thereafter. Nuclear run-on transcription assays showed that induction of junB by TGF-β occurred at the level of transcription through a mechanism independent of protein synthesis. junB was also induced by 20% fetal bovine serum, platelet-derived growth factor, and insulin, but the maximal level of expression in response to these growth factors was lower and less sustained than in the presence of TGF-β. In contrast to the dramatic effects of TGF-β on junB expression, c-jun showed only a 2.5-fold increase in expression in response to TGF-β. In an effort to identify additional members of the jun family which might be regulated by TGF-β, a cDNA library was prepared from the poly(A)⁺ mRNA of TGF-β-stimulated BC₃H1 myocytes and was screened under conditions of reduced stringency with a v-jun DNA probe. From this screen, a new jun-related gene product was identified which shared a high degree of homology with regions of c-jun and junB which have been implicated in transcriptional activation, dimerization, and DNA binding. The transcript for this jun-related gene was expressed constitutively in BC₃H1 cells and was not regulated by TGF-β. Three members of the jun family thus exhibit distinct responses to TGF-β in BC₃H1 cells. The rapid transcriptional induction of junB is among the earliest and most dramatic responses to TGF-β yet described and suggests that junB may mediate certain of the diverse biological effects of this growth factor.