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.
Keywords: Interaction; MAP; NF-κB; Ran-binding protein in the microtubule-organizing center; RanBPM; TACE; TAK1; TGF-β; TGF-β type I receptor; TGF-β type II receptor; TNF-alpha converting enzyme; TRAF6; TβRI; TβRII; Ubiquitination; mitogen-activated protein; nuclear factor KB; transforming growth factor (TGF)-activated kinase 1; transforming growth factor β; tumor necrosis factor (TNF)-receptor-associated factor 6.
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