v-Src and EJ Ras alleviate repression of c-Jun by a cell-specific inhibitor

Abstract

THE AP-1 family of transcription factors, which includes the proto-oncogene products c-Jun and c-Fos¹, controls the stimulation of cellular genes by growth factors and the expression of oncogenes, including src and ras^2–8. Transcriptional activation by c-Jun is regulated by a cell-type-specific inhibitor that represses the activity of a transcriptional activation domain (Al) of c-Jun by operating through the adjacent negative regulatory region (δ) (refs 9–11). Here we show that cotransfection of the src or ras oncogene enhances the transcriptional activity of a GAL4: c-Jun hybrid that includes the δ-A1 region of c-Jun, suggesting that the DNA binding and dimerization domain of c-Jun is not required for stimulation by Src or Ras. Moreover, induction of c-Jun activity by Src and Ras occurs in cell lines containing the c-Jun inhibitor but not in a cell line lacking it. The region in c-Jun essential for the stimulatory action of these oncogenes maps to domain Al. These findings suggest the existence of signal-transduction pathways that result in an increase in transcriptional activity of c-Jun and AP-1 by disrupting the c-Jun:inhibitor interaction.