The TFG protein, involved in oncogenic rearrangements, interacts with TANK and NEMO, two proteins involved in the NF-kappaB pathway.

TRK-fused gene (TFG) was first identified as a partner of NTRK1 in generating the thyroid TRK-T3 oncogene, and is also involved in oncogenic rearrangements with ALK in anaplastic lymphoma and NOR1 in mixoid chondrosarcoma. The TFG physiological role is still unknown, but the presence of a number of motifs involved in protein interactions suggests that it may function by associating with other proteins. We have recently demonstrated that TFG associates and regulates the activity of the tyrosine phosphatase SHP-1. In this study by yeast two-hybrid screening we identified NEMO and TANK, two proteins modulating the NF-kappaB pathway, as novel TFG-interacting proteins. These interactions were further characterized in vitro and in vivo. We provide evidence that TFG and NEMO may be part of the same high molecular weight complex. TFG enhances the effect of TNF-alpha, TANK, TNF receptor-associated factor (TRAF)2, and TRAF6 in inducing NF-kappaB activity. We suggest that TFG is a novel member of the NF-kappaB pathway. Copyright 2006 Wiley-Liss, Inc.