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The c-ets proto-oncogenes encode transcription factors that cooperate with c-Fos and c-Jun for transcriptional
B Wasylyk1, C Wasylyk, P Flores
1Laboratoire de Génétique Moléculaire des Eucaryotés du CNRS, Strasbourg, France.
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. 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. We show here that the products of the ets-1 and -2 proto-oncogenes, whose biological function was previously unknown, are transcription factors that activate transcription through the PEA 3 motif. The p68c-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 p68c-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.
Insights
Oncogenes activate transcription factors AP-1 and PEA 3. The ets-1 and ets-2 proto-oncogenes encode new transcription factors that bind DNA and activate transcription, cooperating with AP-1 components.
Area of Science:
- Molecular Biology
- Oncology
- Gene Regulation
Background:
- Cell transformation involves altered gene expression.
- Activation of transcription factors AP-1 and PEA 3 is crucial for oncogene-driven transformation.
- Synergistic activity of AP-1 and PEA 3 is required for transcription activation by oncogenes, growth factors, and TPA.
Purpose of the Study:
- To investigate the biological function of ets-1 and ets-2 proto-oncogene products.
- To determine if ets gene products act as transcription factors.
- To elucidate the role of ets proteins in oncogene-mediated gene expression.
Main Methods:
- DNA binding assays to assess protein-DNA interaction.
- Transcriptional activation assays using specific promoter constructs.
- Co-transfection experiments with AP-1 components (c-Fos, c-Jun).
Main Results:
- The products of ets-1 and ets-2 proto-oncogenes are identified as transcription factors.
- These factors activate transcription through the PEA 3 motif.
- The p68c-ets-1 protein binds DNA and possesses a transcriptional activation domain.
- p68c-ets-1 cooperates with c-Fos and c-Jun to activate transcription from the polyoma enhancer.
Conclusions:
- The ets gene family represents a novel class of transcription factors.
- ets proteins play a significant role in regulating gene expression during cell transformation.
- Cooperative action of ets proteins, AP-1, and other oncoproteins may mediate cellular responses to growth stimuli.