Cooperative inhibition of bone morphogenetic protein signaling by Smurf1 and inhibitory Smads
Cooperative inhibition of bone morphogenetic protein signaling by Smurf1 and inhibitory Smads
复制标题
DOI：
10.1091/mbc.e02-07-0441
复制
发表时间：
2003-07-01
影响因子：
3.3
通讯作者：
Imamura, T
中科院分区：
文献类型：
--
作者：
Murakami, G;Watabe, T;Imamura, T
Smad泛素调节因子（Smurf）1与骨形态发生蛋白（BMP）Smad 1/5的受体调节Smads结合，并促进其降解。此外，Smurf 1通过抑制性Smad（I-Smad）Smad 7与转化生长因子β I型受体结合并诱导其降解。在此，我们研究了Smurf 1是否与I-Smads Smad 6/7一起负调节BMP信号传导。Smurf 1和Smad 6协同诱导非洲爪蟾胚胎的次生轴。在哺乳动物细胞中使用BMP响应启动子-报告基因构建体，我们发现Smurf 1与I-Smad在抑制BMP信号传导中合作，并且Smurf 1的抑制活性不一定与其直接结合Smad 1/5的能力相关。Smurf 1通过I-Smads与BMP I型受体结合，并诱导这些受体的泛素化和降解。此外，Smurf 1通过I-Smads与Smad 1/5间接结合，并诱导其泛素化和降解。因此，Smurf 1通过多种机制控制BMP信号传导，无论是否有I-Smads。
Smad ubiquitin regulatory factor (Smurf) 1 binds to receptor-regulated Smads for bone morphogenetic proteins (BMPs) Smad1/5 and promotes their degradation. In addition, Smurf1 associates with transforming growth factor-beta type I receptor through the inhibitory Smad (I-Smad) Smad7 and induces their degradation. Herein, we examined whether Smurf1 negatively regulates BMP signaling together with the I-Smads Smad6/7. Smurf1 and Smad6 cooperatively induced secondary axes in Xenopus embryos. Using a BMP-responsive promoter-reporter construct in mammalian cells, we found that Smurf1 cooperated with I-Smad in inhibiting BMP signaling and that the inhibitory activity of Smurf1 was not necessarily correlated with its ability to bind to Smad1/5 directly. Smurf1 bound to BMP type I receptors via I-Smads and induced ubiquitination and degradation of these receptors. Moreover, Smurf1 associated with Smad1/5 indirectly through I-Smads and induced their ubiquitination and degradation. Smurf1 thus controls BMP signaling with and without I-Smads through multiple mechanisms.