Abstract
Cullin3-based ubiquitin E3 ligases induce ubiquitination of substrates leading to their proteasomal or lysosomal degradation. BTB proteins serve as adaptors by binding to Cullin3 and recruiting substrate proteins, which enables specific recognition of a broad spectrum of targets. Hence, Cullin3 and its adaptors are involved in myriad cellular processes and organ functions. Cullin3-based ubiquitin E3 ligase complexes target small GTPases of the Rho subfamily, which are key regulators of cytoskeletal dynamics and cell adhesion. In this mini review, we discuss recent insights in Cullin3-mediated regulation of Rho GTPases and their impact on cellular function and disease. Intriguingly, upstream regulators of Rho GTPases are targeted by Cullin3 complexes as well. Thus, Rho GTPase signaling is regulated by Cullin3 on multiple levels. In addition, we address current knowledge of Cullin3 in regulating vascular function, focusing on its prominent role in endothelial barrier function, angiogenesis and the regulation of blood pressure.
Highlights
Ubiquitination is an important post-translational modification, which controls a variety of cellular functions
Chen et al (2009) were the first to show that RhoA is targeted by a Cullin3-based ubiquitin E3 ligase and they discovered that a well-conserved family of BTB-domain proteins named BACURDs serve as substrate adaptor proteins (Figure 1C)
Since gamma-aminobutyric acid receptorassociated protein (GABARAP) proteins are covalently attached to lipid membranes, they may recruit the Cullin3-KBTBD6/KBTBD7 complex to intracellular or plasma membranes, locally controlling T-cell Invasion And Migration1 (Tiam1) ubiquitination and restricting Rac1 activation (Palamidessi et al, 2008; Genau et al, 2015)
Summary
Ubiquitination is an important post-translational modification, which controls a variety of cellular functions. Cullin3-based E3 ligases play an important, albeit poorly understood, role in regulating Rho GTPase signaling toward F-actin polymerization and stress fiber formation driving cell adhesion and migration in a variety of cell types. Chen et al (2009) were the first to show that RhoA is targeted by a Cullin3-based ubiquitin E3 ligase and they discovered that a well-conserved family of BTB-domain proteins named BACURDs serve as substrate adaptor proteins (Figure 1C).
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
