Review Article S-Nitrosation and Ubiquitin-Proteasome System Interplay in Neuromuscular Disorders

Copyright © 2014 Salvatore Rizza et al.(is is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. Protein S-nitrosation is deemed as a prototype of posttranslational modi!cations governing cell signaling. It takes place on speci!c cysteine residues that covalently incorporate a nitric oxide (NO) moiety to form S-nitrosothiol derivatives and depends on the ratio between NO produced by NO synthases and nitrosothiol removal catalyzed by denitrosating enzymes. A large number of cysteine-containing proteins are found to undergo S-nitrosation and, among them, the enzymes catalyzing ubiquitination, mainly the class of ubiquitin E3 ligases and the 20S component of the proteasome, have been reported to be redox modulated in their activity. In this review we will outline the processes regulating S-nitrosation and try to debate whether and how it a)ects protein ubiquitination and degradation via the proteasome. In particular, since muscle and neuronal health largely depends on the balance between protein synthesis and breakdown, here we will discuss the impact of S-nitrosation in the e*ciency of protein quality control system, providing lines of evidence and speculating about its involvement in the onset and maintenance of neuromuscular dysfunctions. 1. Redox Modifications and Cell Signaling (e main molecular mechanism underlying signal transduc-tion in eukaryotic cells relies on the regulation of protei