The c-ets proto-oncogenes encode transcription factors that cooperate with c-Fos and c-Jun for transcriptional activation

Abstract

CELL transformation by oncogenes leads to changes in gene expression. A key event in this process seems to be activation of the transcription factors AP-1 and PEA 3 (refs 1–5). Their synergistic activities are required for efficient activation of transcription from different promoters by many different oncogenes, serum growth factors and the tumour promoter TPA^4,5. We show here that the products of the ets-1 and -2 proto-oncogenes, whose biological function was previously unknown^6–11, are transcription factors that activate transcription through the PEA 3 motif. The p68^c-ets-1 protein specifically binds to DNA and contains a transcriptional activation domain. The ets-like gene family therefore seems to encode a new family of transcription factors, apparently unrelated to other transcription factors. The p68^c-ets-1 protein cooperates with c-Fos and c-Jun (components of AP-1) for activation of transcription from the oncogene-responsive domain of the polyoma enhancer, indicating that combined activity of all three oncoproteins could be involved in the response of cells to growth stimuli.