title: A direct way of redox sensing.
abstract: The function and activity of many proteins can be regulated by changes in the intracellular redox potential. This regulation can involve posttranslational modifications mediated by redox-sensitive pathways. A more direct way to sense redox changes is through reversible covalent modification of cysteine residues of proteins by reactive oxygen species (ROS), e.g. H2O2, and reactive nitrogen species (RNS), e.g. NO. Known cysteine modifications include disulfide bonds, S-nitrosylation, S-glutathionylation, as well as sulphenic acid or sulphinic acid formation. Cysteine-based redox switches are difficult to predict because currently the knowledge of precise consensus sequences is limited. One recurrent feature of known redox switches is the close proximity of polar amino acids to the reactive cysteine, resulting in stabilization of the reactive thiolate anion form. There is growing evidence that intracellular thiol-based redox sensing and signaling mechanisms may also be involved in the regulation of RNA-binding proteins. Here, we discuss the concept of cysteine-based redox sensing and signaling, the potential importance of redox switches in RNA-binding proteins and open questions in the field.
authors.affiliation: Novartis Institutes for BioMedical Research, Basel, Switzerland.
authors.forename: Roger
authors.initials: R
authors.lastname: Benoit
authors.forename: Manfred
authors.initials: M
authors.lastname: Auer
mesh_terms: D003545:Cysteine / Q000378:metabolism*; D004220:Disulfides / Q000378:metabolism; D006861:Hydrogen Peroxide / Q000378:metabolism; D010084:Oxidation-Reduction; D018384:Oxidative Stress; D011499:Protein Processing, Post-Translational; D016601:RNA-Binding Proteins / Q000378:metabolism; D026361:Reactive Nitrogen Species / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000378:metabolism; D015398:Signal Transduction; D013438:Sulfhydryl Compounds / Q000378:metabolism*
chemical_list: D004220:Disulfides; D016601:RNA-Binding Proteins; D026361:Reactive Nitrogen Species; D017382:Reactive Oxygen Species; D013438:Sulfhydryl Compounds; D006861:Hydrogen Peroxide; D003545:Cysteine