NOS2 Regulation of NF-κB by S-Nitrosylation of p65*
By Z. T. Kelleher, Akio Matsumoto, J. Stamler, H. E. Marshall. Journal of Biological Chemistry, 2007
216 citations recorded by the source corpus.
Signal transduction in the NF-κB transcription factor pathway is inhibited by inducible nitric oxide synthase (NOS2) activity, although the molecular mechanism(s) are incompletely understood. We have previously shown that nitric oxide (NO), derived from NOS2 consequent upon cytokine stimulation, attenuates NF-κB p50-p65 heterodimer DNA binding and have identified the p50 monomer as a locus for inhibitory S-nitrosylation. We now show that the binding partner of p50, NF-κB p65, is also targeted by NO following cytokine stimulation of respiratory epithelial cells and macrophages and identify a conserved cysteine within the Rel homology domain that is the site for S-nitrosylation. S-Nitrosylation of p65 inhibits NF-κB-dependent gene transcription, and nuclear levels of S-nitrosylated p65 correlate with decreased DNA binding of the p50-p65 heterodimer. NOS2 regulates cytokine-induced S-nitrosylation of p65, resulting in decreased NF-κB binding to the NOS2 promoter, thereby inhibiting further NOS2 expression. Collectively, these findings delineate a mechanism by which NOS2 modulates NF-κB activity and regulates gene expression in inflammation.
Subfields: Immunology, Physiology
View Paper: https://www.semanticscholar.org/paper/f6d231979a37b33bdc4a02ada96b5d048bf08d82
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In Physiology
Citations in the corpus
- Hydrogen sulfide-linked sulfhydration of NF-κB mediates its anti-apoptotic actions (2012, background): “As sulfhydration and nitrosylation of p65 respectively stimulate and inhibit (Kelleher et al., 2007) its transcriptional activity, we measuredDNAbinding affinity of p65byChIPassay (FigureS6A).”