title: The TFG-TEC fusion gene created by the t(3;9) translocation in human extraskeletal myxoid chondrosarcomas encodes a more potent transcriptional activator than TEC.
abstract: The t(3;9)(q11-q12;q22) translocation associated with human extraskeletal myxoid chondrosarcomas results in a chimeric molecule in which the N-terminal domain (NTD) of the TFG (TRK-fused gene) is fused to the TEC (Translocated in Extraskeletal Chondrosarcoma) gene. Little is known about the biological function of TFG-TEC. Because the NTDs of TFG-TEC and TEC are structurally different, and the TFG itself is a cytoplasmic protein, the functional consequences of this fusion in extraskeletal myxoid chondrosarcomas were examined. The results showed that the chimeric gene encoded a nuclear protein that bound DNA with the same sequence specificity as the parental TEC protein. Comparison of the transactivation properties of TFG-TEC and TEC indicated that the former has higher transactivation activity for a known target reporter containing TEC-binding sites. Additional reporter assays for TFG (NTD) showed that the TGF (NTD) of TFG-TEC induced a 12-fold increase in the activation of luciferase from a reporter plasmid containing GAL4 binding sites when fused to the DNA-binding domain of GAL4, indicating that the TFG (NTD) of the TFG-TEC protein has intrinsic transcriptional activation properties. Finally, deletion analysis of the functional domains of TFG (NTD) indicated that the PB1 (Phox and Bem1p) and SPYGQ-rich region of TFG (NTD) were capable of activating transcription and that full integrity of TFG (NTD) was necessary for full transactivation. These results suggest that the oncogenic effect of the t(3;9) translocation may be due to the TFG-TEC chimeric protein and that fusion of the TFG (NTD) to the TEC protein produces a gain-of-function chimeric product.
authors.affiliation: Laboratory of Molecular and Cellular Biology, Department of Life Science, Sogang University Seoul 121-742, Korea.
authors.forename: Bobae
authors.initials: B
authors.lastname: Lim
authors.forename: Hee Jung
authors.initials: HJ
authors.lastname: Jun
authors.forename: Ah-young
authors.initials: AY
authors.lastname: Kim
authors.forename: Sol
authors.initials: S
authors.lastname: Kim
authors.forename: JeeHyun
authors.initials: J
authors.lastname: Choi
authors.forename: Jungho
authors.initials: J
authors.lastname: Kim
mesh_terms: D001483:Base Sequence; D002467:Cell Nucleus / Q000378:metabolism; D002813:Chondrosarcoma / Q000235:genetics*; D002893:Chromosomes, Human, Pair 3; D002899:Chromosomes, Human, Pair 9; D017931:DNA Primers; D024202:Electrophoretic Mobility Shift Assay; D050939:Gene Fusion; D006801:Humans; D011505:Protein-Tyrosine Kinases / Q000235:genetics* / Q000378:metabolism; D011506:Proteins / Q000235:genetics* / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015534:Trans-Activators / Q000235:genetics*; D014178:Translocation, Genetic; D033921:Vesicular Transport Proteins
chemical_list: D017931:DNA Primers; D011505:Protein-Tyrosine Kinases; D011506:Proteins; D015534:Trans-Activators; C096163:TFG protein, human; D033921:Vesicular Transport Proteins; C089848:Tec protein-tyrosine kinase