JUNB PROMOTER REGULATION - RAS MEDIATED TRANSACTIVATION BY C-ETS-1 AND C-ETS-2

The Jun gene family encode components of the AP-1 transcription factor complex that regulate a variety of TRE-containing target promoters. E xpression of family members is induced by a wide variety of extracellu lar stimuli and thought to be important in mediating cellular prolifer ation and differentiation. We have localized cis-acting; DNA sequences in the murine junB promoter capable of mediating transcriptional acti vation by the proto-oncogene products c-Ets-l and c-Ets-2. We show by promoter deletion analysis that multiple elements located between - 84 8 and - 574, and between - 196 and - 91 can mediate transactivation by ETS-family members in different cell types. In vitro DNA binding assa ys indicate that the elements identified can specifically interact wit h c-Ets-1 protein. Furthermore, we show that ETS-transactivation of a variety of reporter constructs is dramatically enhanced by introductio n of oncogenic Ha-ras. The activation of Pas by extracellular stimuli invokes a phosphorylation cascade that includes the downstream mitogen -activated protein (MAP) kinase p44(ERK-1). W,further show that additi on of activated p44(ERK-1) MAP kinase can also enhance ETStransactivat ion of junB promoter reporter constructs. Here we propose that ETS-fam ily members play a role in the activation of junB transcription by a R as-stimulated signal transducing pathway that includes MAP kinase(s).