State Key Laboratory of Proteomics, Department of Genomics and Proteomics, Beijing Proteome Research Center, Beijing Institute of Radiation Medicine, Beijing, China.
Mol Cell Biochem. 2010 May;338(1-2):11-7. doi: 10.1007/s11010-009-0315-y. Epub 2009 Nov 24.
The HECT-type E3 Smad ubiquitination regulation factor 1 (Smurf1) functions in regulation of cell polarity and bone homeostasis by targeting Smads, Runx2, RhoA and MEKK2 for ubiquitination and degradation. In a yeast two-hybrid screening, we identified TNF receptor-associated factor 4 (TRAF4) as a candidate substrate and was further validated. The PY motifs of TRAF4 mediated the interaction with the second WW domain of Smurf1. Overexpression of Smurf1 reduced the protein levels of TRAF4 dependent of its E3 activity and the proteasome. Further, we showed that all six members of TRAF family could be ubiquitinated by Smurf1. Consequently, Smurf1 interfered with the functions of TRAFs in NF-kappaB signaling under stimulation or not. These results suggested a new role of Smurf1 in inflammation and immunity through controlling the degradation of TRAFs.
HECT 型 E3 Smad 泛素化调节因子 1（Smurf1）通过靶向 Smads、Runx2、RhoA 和 MEKK2 的泛素化和降解，在调节细胞极性和骨稳态中发挥作用。在酵母双杂交筛选中，我们鉴定了 TNF 受体相关因子 4（TRAF4）作为候选底物，并进一步进行了验证。TRAF4 的 PY 基序介导了与 Smurf1 的第二个 WW 结构域的相互作用。Smurf1 的过表达降低了 TRAF4 的蛋白水平，这依赖于其 E3 活性和蛋白酶体。此外，我们表明 Smurf1 可以泛素化 TRAF 家族的所有六个成员。因此，Smurf1 在刺激或不刺激的情况下通过干扰 TRAFs 在 NF-κB 信号转导中的功能来发挥作用。这些结果表明 Smurf1 通过控制 TRAFs 的降解在炎症和免疫中发挥了新的作用。
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