RanBPM interacts with TβRI, TRAF6 and curbs TGF induced nuclear accumulation of TβRI

Transforming growth factor β (TGF-β), a cytokine, and its receptors play a vital role during normal embryogenesis, cell proliferation, differentiation, apoptosis and migration. Ran-binding protein in the microtubule-organizing center (RanBPM) serves as a scaffold protein that has been shown to interact with many other proteins, such as MET, Axl/Sky, TRAF6, IFNR, TrKA and TrkB in addition to p75NTR. In the current study, we have identified RanBPM as a novel binding partner of TβRI by yeast two-hybrid assay. The TβRI and RanBPM association was confirmed by co-immunoprecipitation and GST pull-down experiments. Additionally, expression of RanBPM abrogated the interaction between TβRI and TRAF6. Furthermore, RanBPM could depress TGF-β induced TRAF6 ubiquitination, subsequent NF-κB signaling pathway, and block TGF-β induced TβRI nuclear accumulation. Taken together, our results reveal that RanBPM may modulate TGF-β-mediated downstream signaling and biological functions.