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: Y Labelle, J Bussières, F Courjal, M B Goldring
• Journal: Oncogene (Oncogene) Vol. 18 Issue 21 Pg. 3303-8 (May 27 1999) ISSN: 0950-9232 [Print] England
• PMID: 10359536 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• DNA-Binding Proteins
• EWS-TEC fusion protein, human
• NR4A1 protein, human
• Neoplasm Proteins
• Nuclear Receptor Subfamily 4, Group A, Member 1
• Oncogene Proteins, Fusion
• Protein Isoforms
• Receptors, Cytoplasmic and Nuclear
• Receptors, Steroid
• Trans-Activators
• Transcription Factors

Topics

• Animals
• Artificial Gene Fusion
• COS Cells
• Chondrosarcoma (genetics, metabolism)
• Chromosomes, Human, Pair 22
• Chromosomes, Human, Pair 9
• DNA-Binding Proteins (metabolism)
• Humans
• Neoplasm Proteins (genetics, metabolism)
• Nuclear Receptor Subfamily 4, Group A, Member 1
• Oncogene Proteins, Fusion (genetics, metabolism)
• Protein Isoforms
• Receptors, Cytoplasmic and Nuclear (genetics, metabolism)
• Receptors, Steroid
• Response Elements (genetics)
• Sarcoma, Ewing (metabolism)
• Trans-Activators (genetics, metabolism)
• Transcription Factors (metabolism)
• Translocation, Genetic