Smurf1 interacts with transforming growth factor-beta type I receptor through Smad7 and induces receptor degradation

Smad7 is an inhibitory Smad that acts as a negative regulator of signaling by the transforming growth factor-beta (TGF-beta) superfamily proteins. Sma d7 is induced by TGF-beta, stably interacts with activated TGF-beta type I receptor (T betaR-I), and interferes with the phosphorylation of receptor-r egulated Smads. Here we show that Smurf1, an E3 ubiquitin ligase for bone m orphogenetic protein-specific Smads, also interacts with Smad7 and induces Smad7 ubiquitination and translocation into the cytoplasm. In addition, Smu rf1 associates with T betaR-I via Smad7, with subsequent enhancement of tur nover of T betaR-I and Smad7. These results thus reveal a novel function of Smad7, i.e. induction of degradation of T betaR-I through recruitment of a n E3 ligase to the receptor.