Smurf1 interacts with transforming growth factor-β type I receptor through Smad7 and induces receptor degradation
Smurf1 interacts with transforming growth factor-β type I receptor through Smad7 and induces receptor degradation
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DOI：
10.1074/jbc.c100008200
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发表时间：
2001-04-20
影响因子：
4.8
通讯作者：
Miyazono, K
中科院分区：
文献类型：
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作者：
Ebisawa, T;Fukuchi, M;Miyazono, K
Smad7 是一种抑制性 Smad，可作为转化生长因子-β (TGF-β) 超家族蛋白信号传导的负调节因子。 Smad7 由 TGF-β 诱导，与激活的 TGF-β I 型受体 (T betaR-I) 稳定相互作用，并干扰受体调节的 Smad 的磷酸化。在这里，我们发现 Smurf1（一种用于骨形态发生蛋白特异性 Smad 的 E3 泛素连接酶）也与 Smad7 相互作用，并诱导 Smad7 泛素化并易位到细胞质中。此外，Smurf1 通过 Smad7 与 T betaR-I 结合，随后增强 T betaR-I 和 Smad7 的周转。因此，这些结果揭示了 Smad7 的新功能，即通过向受体招募 E3 连接酶来诱导 T betaR-I 的降解。
Smad7 is an inhibitory Smad that acts as a negative regulator of signaling by the transforming growth factor-beta (TGF-beta) superfamily proteins. Smad7 is induced by TGF-beta, stably interacts with activated TGF-beta type I receptor (T betaR-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 T betaR-I via Smad7, with subsequent enhancement of turnover 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 an E3 ligase to the receptor.