title: Intermolecular disulfide-dependent redox signalling.
abstract: Until recently, ROS (reactive oxygen species) were often seen as merely damaging agents. However, small, but significant, amounts of hydrogen peroxide (H2O2) are also being produced upon, for instance, NADPH-oxidase activation in response to growth factor signalling and as a by-product of mitochondrial respiration. H2O2 perturbs the local cellular redox state and this results in specific and reversible cysteine oxidation in target proteins, thereby translating the redox state into a signal that ultimately leads to an appropriate cellular response. This phenomenon of signalling through cysteine oxidation is known as redox signalling and has recently been shown to be involved in a wide range of physiological processes. Cysteine residue oxidation can lead to a range of post-translational modifications, one of which is the formation of intermolecular disulfides. In the present mini-review we will give a number of examples of proteins regulated by intermolecular disulfides and discuss a recently developed method to screen for these interactions. The consequences of the regulation of the FOXO4 (forkhead box O4) transcription factor by formation of intermolecular disulfides with both TNPO1 (transportin 1) and p300/CBP [CREB (cAMP-response-element-binding protein)-binding protein] are discussed in more detail.
authors.affiliation: *Molecular Cancer Research, Center for Molecular Medicine, University Medical Center Utrecht, Universiteitsweg 100, 3584CG Utrecht, The Netherlands.
authors.forename: Marrit
authors.initials: M
authors.lastname: Putker
authors.affiliation: *Molecular Cancer Research, Center for Molecular Medicine, University Medical Center Utrecht, Universiteitsweg 100, 3584CG Utrecht, The Netherlands.
authors.forename: Harmjan R
authors.initials: HR
authors.lastname: Vos
authors.affiliation: *Molecular Cancer Research, Center for Molecular Medicine, University Medical Center Utrecht, Universiteitsweg 100, 3584CG Utrecht, The Netherlands.
authors.forename: Tobias B
authors.initials: TB
authors.lastname: Dansen
mesh_terms: D000818:Animals; D003545:Cysteine / Q000737:chemistry / Q000378:metabolism*; D004220:Disulfides / Q000378:metabolism*; D051858:Forkhead Transcription Factors / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D010084:Oxidation-Reduction; D015398:Signal Transduction
chemical_list: D004220:Disulfides; D051858:Forkhead Transcription Factors; D003545:Cysteine