Acute Lung Injury Center of Excellence, Division of Pulmonary, Asthma, and Critical Care Medicine, Department of Medicine, The University of Pittsburgh, Pittsburgh, PA, 15213, USA.
Xiangya Hospital of Central South University, Changsha, 410008, China.
Protein Cell. 2018 Sep;9(9):754-769. doi: 10.1007/s13238-017-0486-3. Epub 2017 Oct 27.
Maintenance of cell junctions plays a crucial role in the regulation of cellular functions including cell proliferation, permeability, and cell death. Disruption of cell junctions is implicated in a variety of human disorders, such as inflammatory diseases and cancers. Understanding molecular regulation of cell junctions is important for development of therapeutic strategies for intervention of human diseases. Ubiquitination is an important type of post-translational modification that primarily regulates endogenous protein stability, receptor internalization, enzyme activity, and protein-protein interactions. Ubiquitination is tightly regulated by ubiquitin E3 ligases and can be reversed by deubiquitinating enzymes. Recent studies have been focusing on investigating the effect of protein stability in the regulation of cell-cell junctions. Ubiquitination and degradation of cadherins, claudins, and their interacting proteins are implicated in epithelial and endothelial barrier disruption. Recent studies have revealed that ubiquitination is involved in regulation of Rho GTPases' biological activities. Taken together these studies, ubiquitination plays a critical role in modulating cell junctions and motility. In this review, we will discuss the effects of ubiquitination and deubiquitination on protein stability and expression of key proteins in the cell-cell junctions, including junction proteins, their interacting proteins, and small Rho GTPases. We provide an overview of protein stability in modulation of epithelial and endothelial barrier integrity and introduce potential future search directions to better understand the effects of ubiquitination on human disorders caused by dysfunction of cell junctions.
细胞连接的维持对于细胞功能的调节起着至关重要的作用，包括细胞增殖、通透性和细胞死亡。细胞连接的破坏与多种人类疾病有关，如炎症性疾病和癌症。了解细胞连接的分子调节对于开发人类疾病干预的治疗策略非常重要。泛素化是一种重要的翻译后修饰类型，主要调节内源性蛋白质稳定性、受体内化、酶活性和蛋白质-蛋白质相互作用。泛素化受泛素 E3 连接酶的严格调控，并可被去泛素化酶逆转。最近的研究集中在研究蛋白质稳定性在细胞-细胞连接调节中的作用。钙黏蛋白、紧密连接蛋白及其相互作用蛋白的泛素化和降解与上皮和内皮屏障的破坏有关。最近的研究表明，泛素化参与调节 Rho GTPases 的生物学活性。综上所述，泛素化在调节细胞连接和运动中起着关键作用。在这篇综述中，我们将讨论泛素化和去泛素化对细胞连接中关键蛋白的稳定性和表达的影响，包括连接蛋白、它们的相互作用蛋白和小 Rho GTPases。我们概述了蛋白质稳定性在调节上皮和内皮屏障完整性中的作用，并介绍了潜在的未来研究方向，以更好地理解泛素化对细胞连接功能障碍引起的人类疾病的影响。
