Nitric oxide as a regulator of gene expression: studies with the transcription factor proteins cJun and p50

Both oxidative and nitrosative stresses may result in the inactivation of the binding to DNA of redox-sensitive transcription factors. The underlying biochemical mechanisms may involve oxidation or nitrosylation of critical thiols within the DNA binding domains of these proteins. However, S-glutahionylation, the formation of a mixed disulfide between glutathione and the redox-sensitive cysteine residues, has been shown to occur under NO exposure and pro-oxidative conditions in c-Jun, one of the AP-1 constituents. This modification may be functionally important as it is reversible and has been detected in other transcription factors, such as NF-kappaB, by using covalent chromatography with a modified S-nitrosoglutathione sepharose.