Abstract
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.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Carrier Proteins / genetics
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Carrier Proteins / metabolism*
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Genes, Tumor Suppressor
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Heterogeneous-Nuclear Ribonucleoproteins
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Humans
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Oncogene Proteins, Fusion / genetics
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Oncogene Proteins, Fusion / metabolism*
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Proto-Oncogene Protein c-fli-1
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RNA-Binding Protein EWS
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Ribonucleoproteins / genetics
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Ribonucleoproteins / metabolism*
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Sarcoma, Ewing / genetics
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Sarcoma, Ewing / metabolism*
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Transcription Factors / genetics
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Transcription Factors / metabolism*
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Tumor Cells, Cultured
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Tumor Suppressor Proteins*
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Ubiquitin-Protein Ligases*
Substances
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Carrier Proteins
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EWS-FLI fusion protein
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Heterogeneous-Nuclear Ribonucleoproteins
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Oncogene Proteins, Fusion
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Proto-Oncogene Protein c-fli-1
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RNA-Binding Protein EWS
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Ribonucleoproteins
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Transcription Factors
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Tumor Suppressor Proteins
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BARD1 protein, human
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Ubiquitin-Protein Ligases