E1AF, an ets-family transcription factor, interacts with Daxx to induce apoptosis

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E1AF is a transcription factor that binds to the enhancer of the adenovirus E1A gene. Sequence analysis showed homology with the Ets-domain and E1AF is a human homologue of mouse PEA3 that is a subgroup of ets-oncogene family. We have reported that E1AF can upregulate multiple matrix metalloproteinase genes that concerns cancer cell invasion/metastasis in oral squamous cell carcinoma and lung carcinoma. On the other hand, we have also reported that E1AF can activate p21waf1/cip1, a cell cycle inhibitory factor, promoter. Daxx was originally identified as an apoptosis inducing molecule that act in the Fas downstream pathway. Recently, Daxx was shown to suppress the ets-1 transcriptional activity, and thought to act as a transcriptional reppressor. We investigated the interaction between E1AF and Daxx. GST-pull down assay revealed that E1AF bound to Daxx, that was confirmed by in vivo experiments using 293 cells. The transcriptional activity of E1AF was not affected by Daxx; however, apoptotic cell death was induced in 293 cells and H1299 cells by co-transfection with E1AF and Daxx. The localization of Daxx and E1AF was investigated using con-focal laser microscopy. Co-localization of E1AF and Daxx was observed and E1AF altered the Daxx localization from nucleus to cytoplasm. These results indicate that E1AF has the ability to induce apoptosis by altering the Daxx localization.