We would like to thank Vincent Récamier, Raphaël Voituriez, Leonid Mirny, Yitzhak Rabin, Lana Bosanac and Benjamin Guglielmi for stimulating discussions. We also acknowledge financial support from the following grants: ANR-12-BSV8-0015 and ANR-10-LABX-54. “
“Modification of cysteine residues by reactive oxygen species (ROS), reactive nitrogen species (RNS) and electrophiles has emerged as a significant means of altering the structure and function of many proteins [1, 2, 3, 4, 5 and 6]. Reversible oxidation

of certain protein thiol groups plays key signaling ZD1839 mouse roles in a range of physiological processes, for example in the regulation of tyrosine phosphatase activity [7], the redox regulation of transcription factors [8] and in T cell activation during the immune response [9]. The reactivity of protein thiols with ROS, RNS and electrophiles additionally underlies selleckchem their important role in defense against oxidative damage and xenobiotics [1, 2, 3, 4, 5 and 10].

In all of these processes there are a broad range of reactions that can occur to the cysteine thiol (Figure 1). Whether a modification occurs depends on a number of factors including the local environment of the cysteine residue, its proximity to the relevant reactive species, its pKa, solvent exposure and subcellular location [ 1, 6, 11 and 12••]. Additionally, some of these cysteine modifications are reversible by the action of reductive processes through the thioredoxin

and glutathione systems [ 13 and 14]. Reversible thiol modifications include glutathionylation [ 15], mixed disulfide formation with low molecular weight thiols, sulfenic acid formation [ 3], S-nitrosation (S-nitrosylation) [ 16], S-acylation [ 17], sulfenylamide formation [ 18], and the generation of intraprotein and interprotein disulfides [ 19 and 20]. In addition to reversible modifications, there are a number of cysteine adducts that can form irreversibly due about to reactions with electrophiles, which generally produce thioether products [ 10]. Similarly, the prolonged exposure of cysteine residues to ROS and RNS can also lead to the formation of irreversibly modified forms, such as sulfinic or sulfonic acids [ 21 and 22]. These protein modifications may contribute to oxidative damage, to the defense against oxidative stress and xenobiotics, or be part of redox signaling pathways. Consequently, it is of interest to be able to identify both the proteins and the cysteine residues affected, to determine the nature of the modification to the cysteine residue and to quantify the extent of the modification occurring during pathology or redox signaling.