On and off: proteasome and TGF-β signaling

Abstract Transforming growth factor-β (TGF-β) signaling mainly relies on the TGF-β receptor–Smad pathway. Meanwhile, TGF-β binding to its receptors initiates the degradation of several key components of its signaling pathway. The degradation of these components, including both positive and negative transducers, is mediated by the ubiquitin–proteasome system. Inhibition of the proteasome activity causes accumulation of these components in the cells and modulates TGF-β signaling in a time-dependent and gene-specific manner. The accelerated degradation of TGF-β signaling components via the proteasome system has been found in a number of tumors, indicating that dysregulated proteasomal degradation is a novel pathway how tumor cells silence TGF-β signaling.

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