Ubiquitin links to cytoskeletal dynamics, cell adhesion and migration

Department of Molecular Cell Biology, Sanquin Research and Landsteiner Laboratory, Academic Medical Center, University of Amsterdam, Plesmanlaan 125, 1066 CX Amsterdam, The Netherlands.
Biochemical Journal (Impact Factor: 4.4). 02/2012; 442(1):13-25. DOI: 10.1042/BJ20111815
Source: PubMed


Post-translational modifications are used by cells to link additional information to proteins. Most modifications are subtle and concern small moieties such as a phosphate group or a lipid. In contrast, protein ubiquitylation entails the covalent attachment of a full-length protein such as ubiquitin. The protein ubiquitylation machinery is remarkably complex, comprising more than 15 Ubls (ubiquitin-like proteins) and several hundreds of ubiquitin-conjugating enzymes. Ubiquitin is best known for its role as a tag that induces protein destruction either by the proteasome or through targeting to lysosomes. However, addition of one or more Ubls also affects vesicular traffic, protein-protein interactions and signal transduction. It is by now well established that ubiquitylation is a component of most, if not all, cellular signalling pathways. Owing to its abundance in controlling cellular functions, ubiquitylation is also of key relevance to human pathologies, including cancer and inflammation. In the present review, we focus on its role in the control of cell adhesion, polarity and directional migration. It will become clear that protein modification by Ubls occurs at every level from the receptors at the plasma membrane down to cytoskeletal components such as actin, with differential consequences for the pathway's final output. Since ubiquitylation is fast as well as reversible, it represents a bona fide signalling event, which is used to fine-tune a cell's responses to receptor agonists.

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Available from: Micha Nethe, Dec 24, 2013
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    • "The proteins of the ubiquitination machinery comprise several ubiquitin-like proteins and hundreds of ubiquitin-conjugating enzymes. Ubiquitin is mainly known for its role as a tag that induces protein degradation either by the proteasome or through targeting to lysosomes, but it is well established that ubiquitination is also a component of most cellular signaling pathways for the control of cell adhesion, polarity and directional migration (Schaefer et al. 2012). Most of the in silico predicted functions of RPHM21 such as reorganization of cytoskeleton, cell migration, cell cycle control, chromatin remodeling, and transcriptional control are shared with MK3 (Ronkina et al. 2008; Milani, Ghiselli, Guerra, et al. 2013). "
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    • "Thus, it is the balance between the opposing actions of specific E3 ligases and DUBs which ultimately determines the ubiquitination status of a given target, rendering protein ubiquitination a versatile and dynamic posttranslational modification. The list of cellular processes where ubiquitination plays a regulatory role is continuously expanding, and includes gene expression [16], cell cycle progression [17], apoptosis [18], DNA repair [19] and cell motility [20], among others. Many of these ubiquitination-regulated processes are essential for maintaining cellular homeostasis, and their alteration contributes to tumor development. "
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