Smurf1 Interacts with Transforming Growth Factor-β Type I Receptor through Smad7 and Induces Receptor Degradation*

By Takanori Ebisawa, Minoru Fukuchi, Gyo Murakami, T. Chiba, Keiji Tanaka, T. Imamura, K. Miyazono. Journal of Biological Chemistry, 2001

911 citations recorded by the source corpus.

Smad7 is an inhibitory Smad that acts as a negative regulator of signaling by the transforming growth factor-β (TGF-β) superfamily proteins. Smad7 is induced by TGF-β, stably interacts with activated TGF-β type I receptor (TβR-I), and interferes with the phosphorylation of receptor-regulated Smads. Here we show that Smurf1, an E3 ubiquitin ligase for bone morphogenetic protein-specific Smads, also interacts with Smad7 and induces Smad7 ubiquitination and translocation into the cytoplasm. In addition, Smurf1 associates with TβR-I via Smad7, with subsequent enhancement of turnover of TβR-I and Smad7. These results thus reveal a novel function of Smad7, i.e. induction of degradation of TβR-I through recruitment of an E3 ligase to the receptor.

Subfields: Molecular Biology

View Paper: https://www.semanticscholar.org/paper/3fb925044ad8a3706f08ee09714a8d7ae81e0ed3

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Citations in the corpus

SPECIFICITY AND VERSATILITY IN TGF-β SIGNALING THROUGH SMADS (2005, background): “Smad6 and Smad7 also inhibit TGF-β family signaling by interacting directly with Smurf E3 ubiquitin ligases and mobilizing these ligases to the type I receptors, leading to proteasomal degradation of the receptors (Ebisawa et al. 2001, Kavsak et al. 2000, Murakami et al. 2003).”
The basics of epithelial–mesenchymal transition (EMT): A study from a structure, dynamics, and functional perspective (2019, background): “I, and the inhibitory SMAD and SMAD7, which prevent the phosphorylation of SMAD2/3 (Datta & Moses, 2000; Ebisawa et al., 2001; Kavsak et al., 2000; Massagué & Gomis, 2006) and induces the degradation of TGF‐β receptors (Ibarrola et al., 2004; Koinuma et al., 2003).”
Diverse Roles of TGF-β/Smads in Renal Fibrosis and Inflammation (2011, background): “In chronic kidney diseases, TGF-β1 and angiotensin II are able to induce Smad7 mRNA expression and also activate the Smurfs and arkadia-dependent ubiquitin–proteasome pathways that, in turn, degrade Smad7 protein via a post-transcriptional modification mechanism [7, 8, 37, 68, 69].”
Genetic Analysis of the Mammalian Transforming Growth Factor-β Superfamily (2002, background): “In mammalian cells and parallel to SMURF2, SMURF1 interacts with SMAD7 to cause translocation of the complex to the cytoplasm, in which the complex will bind to the T RI where it enhances ubiquination of both T RI and SMAD7, thereby inducing turnover of these two proteins (130).”
TGF-β/Smad signaling in renal fibrosis (2015, background): “…be induced by a Smad3-dependent mechanism, Frontiers in Physiology | www.frontiersin.org 2 March 2015 | Volume 6 | Article 82 which in turn blocks the signal transduction of TGF-β1 via its negative feedback loop (Afrakhte et al., 1998; Zhu et al., 1999; Kavsak et al., 2000; Ebisawa et al., 2001).”