Binding of RhoA by the C2 domain of E3 ligase Smurf1 is essential for Smurf1‐regulated RhoA ubiquitination and cell protrusive activity
Binding of RhoA by the C2 domain of E3 ligase Smurf1 is essential for Smurf1‐regulated RhoA ubiquitination and cell protrusive activity
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DOI：
10.1016/j.febslet.2011.06.016
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发表时间：
2011-07
期刊：
影响因子：
3.5
通讯作者：
Maoyuan Tian;C. Bai;Qi Lin;Huayue Lin;Mingdong Liu;Feng Ding;Hong-Rui Wang
中科院分区：
文献类型：
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作者：
Maoyuan Tian;C. Bai;Qi Lin;Huayue Lin;Mingdong Liu;Feng Ding;Hong-Rui Wang
Smurf1介导的RhoA泛素化和降解在调节细胞极性和增殖活性中起着关键作用。然而，Smurf1如何识别RhoA仍然不清楚。在这里，我们报告说，C2结构域的Smurf1是必要的和足够的结合RhoA，因此是至关重要的靶向RhoA的泛素化。与此相反，C2结构域是Smurf1介导的Smad1泛素化。与其生物化学特异性一致，C2结构域对于Smurf1调节的突起形成而不是BMP信号传导是必不可少的。因此，我们的研究揭示了Smurf1的C2结构域在底物选择中的作用机制。蛋白质相互作用的结构总结：SMURF 1通过下拉与Smad 1发生物理相互作用（查看相互作用）SMURF 1通过下拉与RhoA发生物理相互作用（查看相互作用）SMURF 1通过抗标签免疫共沉淀与Smad 1发生物理相互作用（查看相互作用）SMURF 1通过抗标签免疫共沉淀与RhoA发生物理相互作用（查看相互作用）
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. STRUCTURED SUMMARY OF PROTEIN INTERACTIONS: SMURF1physically interactswithSmad1 by pull down(View interaction) SMURF1physically interactswithRhoA by pull down(View interaction) SMURF1physically interactswithSmad1 by anti tag coimmunoprecipitation(View interaction) SMURF1physically interactswithRhoA by anti tag coimmunoprecipitation(View interaction)