Smad ubiquitin regulatory factor 2 (Smurf2), an essential negative regulator of TGF-β signaling, ubiquitinates TGF-β receptors (TβRs) and Smad proteins, inducing their proteasomal degradation. Smurf2 plays crucial roles in regulating TGF-β signaling and maintaining normal cellular functions and tissue homeostasis; dysfunction of Smurf2 triggers abnormal TGF-β signaling in pathological states. Smurf2 has been reported as a potentially strong candidate for targeting therapies for related diseases. Recent work has begun to focus on the regulation of Smurf2 itself, and emerging evidence indicates that Smurf2 is regulated by post-translational modifications (PTMs) mechanisms. These mechanisms predominantly regulate the expression level and E3 ligase activity of Smurf2, strongly suggesting that this protein contributes to complicated roles under multiple pathophysiological conditions. In this review, we cover some significant and novel mechanisms of the PTMs that potentially control Smurf2 participation in TGF-β signaling, including ubiquitylation, SUMOylation, neddylation, phosphorylation, and methylation in order to provide a broad view of the depth and sophistication of Smurf2 function in TGF-β regulation, as well as perspectives for future therapeutic directions for its associated diseases.

Smad泛素调节因子2（Smurf2）是TGF-β信号转导的必不可少的负调节剂，可泛化TGF-β受体（TβRs）和Smad蛋白，诱导其蛋白酶体降解。Smurf2在调节TGF-β信号传导并维持正常的细胞功能和组织动态平衡方面起着至关重要的作用。Smurf2的功能异常在病理状态下触发异常的TGF-β信号传导。据报道，Smurf2是针对相关疾病的靶向疗法的潜在强力候选者。最近的工作已开始集中在Smurf2本身的调节上，新出现的证据表明Smurf2受翻译后修饰（PTM）机制的调节。这些机制主要调节Smurf2的表达水平和E3连接酶活性，有力地表明，这种蛋白质在多种病理生理条件下起着复杂的作用。在这篇综述中，我们涵盖了潜在地控制Smurf2参与TGF-β信号传导的PTM的一些重要且新颖的机制，包括泛素化，SUMO酰化，糖基化，磷酸化和甲基化，以便提供Smurf2的深度和复杂性的广阔视野。在TGF-β调控中发挥功能，以及对其相关疾病的未来治疗方向进行展望。