Interaction of the EWS NH2 terminus with BARD1 links the Ewing's sarcoma gene to a common tumor suppressor pathway.
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.
Spahn
Laura
L
Children's Cancer Research Institute, St. Anna Kinderspital, 1090 Vienna, Austria.
Petermann
Robert
R
Siligan
Christine
C
Schmid
Johannes A
JA
Aryee
Dave N T
DN
Kovar
Heinrich
H
D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism*; D016147:Genes, Tumor Suppressor; D034441:Heterogeneous-Nuclear Ribonucleoproteins; D006801:Humans; D015514:Oncogene Proteins, Fusion / Q000235:genetics / Q000378:metabolism*; D051789:Proto-Oncogene Protein c-fli-1; D034802:RNA-Binding Protein EWS; D012261:Ribonucleoproteins / Q000235:genetics / Q000378:metabolism*; D012512:Sarcoma, Ewing / Q000235:genetics / Q000378:metabolism*; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*; D014407:Tumor Cells, Cultured; D025521:Tumor Suppressor Proteins; D044767:Ubiquitin-Protein Ligases
D002352:Carrier Proteins; C106031:EWS-FLI fusion protein; D034441:Heterogeneous-Nuclear Ribonucleoproteins; D015514:Oncogene Proteins, Fusion; D051789:Proto-Oncogene Protein c-fli-1; D034802:RNA-Binding Protein EWS; D012261:Ribonucleoproteins; D014157:Transcription Factors; D025521:Tumor Suppressor Proteins; C102449:BARD1 protein, human; D044767:Ubiquitin-Protein Ligases