Department of Cardiology, the First Hospital of China Medical University, Shenyang, China.
Center of Reproductive Medicine, Shengjing Hospital of China Medical University, Shenyang, China.
FASEB J. 2023 Aug;37(8):e23110. doi: 10.1096/fj.202300598R.
The ubiquitin-proteasome system is a crucial mechanism for regulating protein levels in cells, with substrate-specific E3 ubiquitin ligases serving as an integral component of this system. Among these ligases are SMAD-specific E3 ubiquitin-protein ligase 1 (SMURF1) and SMAD-specific E3 ubiquitin-protein ligase 2 (SMURF2), which belong to the neural precursor cell-expressed developmentally downregulated 4 (NEDD4) subfamily of Homologous to E6-AP COOH terminus (HECT)-type E3 ligases. As E3 ligases, SMURFs have critical functions in regulating the stability of multiple proteins, thereby maintaining physiological processes such as cell migration, proliferation, and apoptosis. The occurrence of many diseases is attributed to abnormal cell physiology and an imbalance in cell homeostasis. It is noteworthy that SMURFs play pivotal roles in disease progression, with the regulatory functions being complex and either facilitative or inhibitory. In this review, we elucidate the mechanisms by which SMURF1 and SMURF2 can regulate disease progression in non-cancerous diseases. These significant findings offer potential novel therapeutic targets for various diseases and new avenues for research on SMURF proteins.
泛素-蛋白酶体系统是细胞内调节蛋白质水平的关键机制，底物特异性 E3 泛素连接酶是该系统的一个组成部分。这些连接酶包括 SMAD 特异性 E3 泛素蛋白连接酶 1（SMURF1）和 SMAD 特异性 E3 泛素蛋白连接酶 2（SMURF2），它们属于神经前体细胞表达的发育下调 4（NEDD4）亚家族同源 E6-AP COOH 末端（HECT）型 E3 连接酶。作为 E3 连接酶，SMURFs 在调节多种蛋白质稳定性方面具有关键作用，从而维持细胞迁移、增殖和凋亡等生理过程。许多疾病的发生归因于细胞生理异常和细胞内稳态失衡。值得注意的是，SMURFs 在疾病进展中发挥着关键作用，其调节功能复杂，既有促进作用，也有抑制作用。在这篇综述中，我们阐明了 SMURF1 和 SMURF2 如何调节非癌症疾病中的疾病进展的机制。这些重要发现为各种疾病提供了潜在的新治疗靶点，并为 SMURF 蛋白的研究开辟了新途径。
