A TFG-TEC nuclear localization mutant forms complexes with the wild-type TFG-TEC oncoprotein and suppresses its activity

Human extraskeletal myxoid chondrosarcomas (EMCs) are soft tissue tumors characterized by specific chromosomal abnormalities. Recently, a proportion of EMCs were found to harbor a characteristic translocation, t(3;9)(q11-12;q22), involving the TFG (TRK-fused gene) at 3q11-12 and the TEC (Translocated in Extraskeletal Chondrosarcoma) gene at 9q22. The present study used both in vitro and in vivo systems to show that the TFG-TEC protein self-associates, and that this is dependent upon the coiled-coil (CC) domain (aa 97–124), the AF1 domain (aa 275–562), and the DNA-binding domain (DBD) (aa 563–655). The TFG-TEC protein also associated with a mutant NLS-TFG-TEC (AAAA) protein, which harbors mutations in the nuclear localization signal (NLS). Subcellular localization assays showed that the NLS mutant TFG-TEC (AAAA) protein interfered with the nuclear localization of wild-type TFG-TEC. Most importantly, the mutant protein inhibited TFG-TEC-mediated transcriptional activation in vivo. Thus, mutations in the TFG-TEC NLS yield a dominant negative protein. These results show that the biological functions of the TFG-TEC oncogene can be modulated by a dominant negative mutant.
Source: BJ Cell - Category: Biochemistry Authors: Tags: BJ Gene Source Type: research