title: Redox control systems in the nucleus: mechanisms and functions.
abstract: Proteins with oxidizable thiols are essential to many functions of cell nuclei, including transcription, chromatin stability, nuclear protein import and export, and DNA replication and repair. Control of the nuclear thiol-disulfide redox states involves both the elimination of oxidants to prevent oxidation and the reduction of oxidized thiols to restore function. These processes depend on the common thiol reductants, glutathione (GSH) and thioredoxin-1 (Trx1). Recent evidence shows that these systems are controlled independent of the cytoplasmic counterparts. In addition, the GSH and Trx1 couples are not in redox equilibrium, indicating that these reductants have nonredundant functions in their support of proteins involved in transcriptional regulation, nuclear protein trafficking, and DNA repair. Specific isoforms of glutathione peroxidases, glutathione S-transferases, and peroxiredoxins are enriched in nuclei, further supporting the interpretation that functions of the thiol-dependent systems in nuclei are at least quantitatively distinct, and probably also qualitatively distinct, from similar processes in the cytoplasm. Elucidation of the distinct nuclear functions and regulation of the thiol redox pathways in nuclei can be expected to improve understanding of nuclear processes and also to provide the basis for novel approaches to treat aging and disease processes associated with oxidative stress in the nuclei.
authors.affiliation: Department of Medicine, Emory University, Atlanta, GA, USA.
authors.forename: Young-Mi
authors.initials: YM
authors.lastname: Go
authors.forename: Dean P
authors.initials: DP
authors.lastname: Jones
mesh_terms: D000818:Animals; D002467:Cell Nucleus / Q000378:metabolism*; D005978:Glutathione / Q000378:metabolism; D006801:Humans; D008954:Models, Biological; D010084:Oxidation-Reduction; D015398:Signal Transduction / Q000235:genetics / Q000502:physiology; D013879:Thioredoxins / Q000378:metabolism
chemical_list: D013879:Thioredoxins; D005978:Glutathione