title: The EWS/TEC fusion protein encoded by the t(9;22) chromosomal translocation in human chondrosarcomas is a highly potent transcriptional activator.
abstract: The EWS/TEC gene fusion generated by the t(9;22) chromosomal translocation found in extraskeletal myxoid chondrosarcomas encodes a fusion protein containing the amino-terminal domain of the EWS protein fused to the whole coding sequence of the orphan nuclear receptor TEC. We have compared the DNA-binding and transcriptional activation properties of various TEC isoforms and the corresponding EWS/TEC fusion proteins. Band-shift experiments show that the full-length TEC receptor can efficiently bind the NGFI-B Response Element (NBRE), whereas an isoform lacking the entire carboxyl-terminal domain of the receptor binds much less efficiently the NBRE. Addition of the amino-terminal domain of EWS to either isoforms does not alter significantly their DNA-binding properties to the NBRE. Co-transfection experiments of COS cells and human chondrocytes indicate that whereas TEC moderately activates transcription from a NBRE-containing promoter, the corresponding EWS/TEC fusion protein is a highly potent transcriptional activator of the same promoter, being approximately 270-fold more active than the native receptor. EWS/TEC may thus exert its oncogenic potential in chrondrosarcomas by activating the transcription of target genes involved in cell proliferation.
authors.affiliation: Unité de recherche en génétique humaine et moléculaire, CHUQ, Québec, Canada.
authors.forename: Y
authors.initials: Y
authors.lastname: Labelle
authors.forename: J
authors.initials: J
authors.lastname: Bussières
authors.forename: F
authors.initials: F
authors.lastname: Courjal
authors.forename: M B
authors.initials: MB
authors.lastname: Goldring
mesh_terms: D000818:Animals; D019677:Artificial Gene Fusion; D019556:COS Cells; D002813:Chondrosarcoma / Q000235:genetics / Q000378:metabolism*; D002892:Chromosomes, Human, Pair 22; D002899:Chromosomes, Human, Pair 9; D004268:DNA-Binding Proteins / Q000378:metabolism*; D006801:Humans; D009363:Neoplasm Proteins / Q000235:genetics / Q000378:metabolism*; D057105:Nuclear Receptor Subfamily 4, Group A, Member 1; D015514:Oncogene Proteins, Fusion / Q000235:genetics / Q000378:metabolism*; D020033:Protein Isoforms; D018160:Receptors, Cytoplasmic and Nuclear / Q000235:genetics / Q000378:metabolism*; D011987:Receptors, Steroid; D020218:Response Elements / Q000235:genetics*; D012512:Sarcoma, Ewing / Q000378:metabolism*; D015534:Trans-Activators / Q000235:genetics / Q000378:metabolism*; D014157:Transcription Factors / Q000378:metabolism*; D014178:Translocation, Genetic
chemical_list: D004268:DNA-Binding Proteins; C119680:EWS-TEC fusion protein, human; C539821:NR4A1 protein, human; D009363:Neoplasm Proteins; D057105:Nuclear Receptor Subfamily 4, Group A, Member 1; D015514:Oncogene Proteins, Fusion; D020033:Protein Isoforms; D018160:Receptors, Cytoplasmic and Nuclear; D011987:Receptors, Steroid; D015534:Trans-Activators; D014157:Transcription Factors