Key Laboratory of the Ministry of Education for Cell Biology and Tumor Cell Engineering, School of Life Sciences, Xiamen University, Xiamen, Fujian, China.
FEBS Lett. 2011 Jul 21;585(14):2199-204. doi: 10.1016/j.febslet.2011.06.016. Epub 2011 Jun 23.
Smurf1-mediated RhoA ubiquitination and degradation plays key roles in regulation of cell polarity and protrusive activity. However, how Smurf1 recognizes RhoA is still not clear. Here we report that the C2 domain of Smurf1 is necessary and sufficient for binding RhoA, and therefore is crucial for targeting RhoA for ubiquitination. In contrast, the C2 domain is dispensable for Smurf1-mediated ubiquitination of Smad1. Consistent with its biochemical specificity, the C2 domain is essential for Smurf1-regulated protrusion formation but not BMP signaling. Therefore, our study reveals the mechanism of the C2 domain of Smurf1 in substrate selection.
Smurf1 介导的 RhoA 泛素化和降解在调节细胞极性和突起活性方面发挥着关键作用。然而，Smurf1 如何识别 RhoA 尚不清楚。在这里，我们报告 Smurf1 的 C2 结构域对于与 RhoA 的结合是必需且充分的，因此对于将 RhoA 靶向泛素化至关重要。相比之下，C2 结构域对于 Smurf1 介导的 Smad1 泛素化是可有可无的。与它的生化特异性一致，C2 结构域对于 Smurf1 调节的突起形成是必需的，但对于 BMP 信号传导则不是必需的。因此，我们的研究揭示了 Smurf1 的 C2 结构域在底物选择中的机制。
