The role of ubiquitination and deubiquitination in the regulation of cell junctions.
The role of ubiquitination and deubiquitination in the regulation of cell junctions.
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DOI：
10.1007/s13238-017-0486-3
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发表时间：
2018-09
期刊：
影响因子：
21.1
通讯作者：
Zhao J
中科院分区：
文献类型：
--
作者：
Cai J;Culley MK;Zhao Y;Zhao J
细胞连接的维持在包括细胞增殖、渗透性和细胞死亡的细胞功能的调节中起着至关重要的作用。细胞连接的破坏涉及多种人类病症，例如炎性疾病和癌症。了解细胞连接的分子调节对于开发用于干预人类疾病的治疗策略是重要的。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连接调节中的作用。钙粘蛋白、密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破坏有关。近年来的研究表明，Rho GTPases的泛素化参与了其生物学活性的调节。综合这些研究，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蛋白质稳定性和细胞-细胞连接中关键蛋白质表达的影响，包括连接蛋白，它们的相互作用蛋白，和小Rho GTPases。我们提供了一个概述蛋白质的稳定性在调节上皮和内皮屏障的完整性，并介绍潜在的未来的搜索方向，以更好地了解泛素化对人类疾病引起的细胞连接功能障碍的影响。
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.
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影响因子：
3.7
作者：
Bheda A;Yue W;Gullapalli A;Whitehurst C;Liu R;Pagano JS;Shackelford J
通讯作者：
Shackelford J
影响因子：
19
作者：
Brasch J;Harrison OJ;Honig B;Shapiro L
通讯作者：
Shapiro L
影响因子：
21.3
作者：
Batlle, E;Sancho, E;de Herreros, AG
通讯作者：
de Herreros, AG
影响因子：
9.2
作者：
Aparicio, Luis A.;Valladares, Manuel;Blanco, Moises;Alonso, Guillermo;Figueroa, Angelica
通讯作者：
Figueroa, Angelica
影响因子：
--
作者：
Brennan K;Offiah G;McSherry EA;Hopkins AM
通讯作者：
Hopkins AM