K. Miranda Culley
Yutong Zhao
Jing Zhao
1. 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
2. Xiangya Hospital of Central South University, Changsha 410008, China
Funds: This work was supported by the National Institutes of Health (R01GM115389 to J.Z. R01 HL112791 and HL131665 to Y.Z.), and American Lung Association Biomedical Research Grant RG350146 (J.Z.). Junting Cai, Marinda K. Culley, Yutong Zhao, and Jing Zhao declares that they have no conflict of interest.
More InformationCorresponding author: Jing Zhao, zhaoj@upmc.edu
Received Date: 2017-08-27
Accepted Date:2017-10-09
Publish Date:2018-01-01
Abstract
Abstract
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.Keywords: cell-cell junctions,
protein stability,
ubiquitination,
deubiquitination,
Rho GTPases
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