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Interaction of the EWS NH₂ Terminus with BARD1 Links the Ewing’s Sarcoma Gene to a Common Tumor Suppressor Pathway¹

Children’s Cancer Research Institute, St. Anna Kinderspital, 1090 Vienna, Austria [L. S., R. P., C. S., D. N. T. A., H. K.], and Department of Vascular Biology and Thrombosis Research, University of Vienna, 1235 Vienna, Austria [J. A. S.]

In 85% of Ewing family tumors, the NH₂ terminus of EWS is fused to the DNA-binding domain of FLI1, an ets transcription factor. The resulting chimeric protein is a strong transcriptional activator with transforming activity. We report that EWS and EWS-FLI1 interact via their common NH₂ terminus with the COOH terminus of BARD1, a putative tumor suppressor, in vitro and in vivo. Because BARD1 associates via its NH₂-terminal RING domain with the breast cancer susceptibility gene BRCA1 that provides a platform for interactions with proteins involved in DNA repair and checkpoint control, our results provide a link between the Ewing’s sarcoma gene product and the genome surveillance complex.

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