title: Modification of EWS/WT1 functional properties by phosphorylation.
abstract: In many human cancers, tumor-specific chromosomal rearrangements are known to create chimeric products with the ability to transform cells. The EWS/WT1 protein is such a fusion product, resulting from a t(11;22) chromosomal translocation in desmoplastic small round cell tumors, where 265 aa from the EWS amino terminus are fused to the DNA binding domain of the WT1 tumor suppressor gene. Herein, we find that EWS/WT1 is phosphorylated in vivo on serine and tyrosine residues and that this affects DNA binding and homodimerization. We also show that EWS/WT1 can interact with, and is a substrate for, modification on tyrosine residues by c-Abl. Tyrosine phosphorylation of EWS/WT1 by c-Abl negatively regulates its DNA binding properties. These results indicate that the biological activity of EWS/WT1 is closely linked to its phosphorylation status.
authors.affiliation: Department of Biochemistry, McGill University, McIntyre Medical Sciences Building, 3655 Drummond Street, Montreal, Quebec H3G 1Y6, Canada.
authors.forename: J
authors.initials: J
authors.lastname: Kim
authors.forename: J M
authors.initials: JM
authors.lastname: Lee
authors.forename: P E
authors.initials: PE
authors.lastname: Branton
authors.forename: J
authors.initials: J
authors.lastname: Pelletier
mesh_terms: D000818:Animals; D019556:COS Cells; D004247:DNA / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000502:physiology*; D016313:Genes, abl; D034441:Heterogeneous-Nuclear Ribonucleoproteins; D010766:Phosphorylation; D034802:RNA-Binding Protein EWS; D012261:Ribonucleoproteins / Q000502:physiology*; D014157:Transcription Factors / Q000502:physiology*; D014443:Tyrosine / Q000378:metabolism; D025721:WT1 Proteins
chemical_list: D004268:DNA-Binding Proteins; D034441:Heterogeneous-Nuclear Ribonucleoproteins; D034802:RNA-Binding Protein EWS; D012261:Ribonucleoproteins; D014157:Transcription Factors; D025721:WT1 Proteins; D014443:Tyrosine; D004247:DNA