We previously identified two novel genes that interact with regulatory elements within the ETS2 promoter. For the first one, the SBF oncogene, we were able to raise monoclonal antibodies which are being used to further analyze its function in relation to ETS2, as well as its oncogenic activity. The second gene, ERP (for ets-repressor-protein) was analyzed to localize its functional domains and was found to contain a transcriptional repressor domain on its carboxy terminus. This domain was successfully transferred to a heterologous binding domain (GAL4) and was found to exhibit the same repressor activity. The tissue and cell cycle specificity of this gene was also analyzed. The ERP gene itself, as well as hybrids of ERP with ERGB and ETS1, was introduced into a number of cell lines in an attempt to reverse the transforming phenotype of ME26 virus and the phenotype created by the EWS/ERGB rearrangement in Ewing's sarcoma cell lines, with very encouraging results. The ability of ERP to repress transcription from the HIV LTR was analyzed in transiently- and stably- transformed cell lines. Finally, we constructed hybrids between the repressor domain of ERP with the NFkappaB transcription factor, as well as the SBF gene, to address their potential as antiviral agents.
