Fig 7.

Schema of the context-dependent nuclear translocation of TβRI. In our proposed model, TGF-β induces transient interaction between TβRI and Smad2/3, followed by their complexation with importin β1 and nucleolin in the cytoplasm. Consequently, the nuclear transport of TβRI can be initiated at a certain degree in both normal and cancer cells. However, upon nuclear entry, efficient release of the TβRI cargo into the nucleus requires a high level of RanGTP, which is observed only in HER2-transformed cells and HER2-negative cancer cells and not in untransformed cells. Once accumulated in the nucleus, TβRI dissociates from Smad2/3 and binds to the G/A-rich motif in RNA targets in synergy with hnRNP A1, exerting a regulatory function in RNA processing.