Hydrogen sulfide-linked sulfhydration of NF-κB mediates its anti-apoptotic actions

By N. Sen, B. Paul, Moataz M. Gadalla, A. Mustafa, T. Sen, Risheng Xu, Seyun Kim, S. Snyder. Molecules and Cells, 2012

692 citations recorded by the source corpus.

Summary Nuclear factor κB (NF-κB) is an anti-apoptotic transcription factor. We show that the anti-apoptotic actions of NF-κB are mediated by hydrogen sulfide (H2S) synthesized by cystathionine gamma-lyase (CSE). TNFα treatment triples H2S generation by stimulating binding of SP1 to the CSE promoter. H2S generated by CSE stimulates DNA binding and gene activation of NF-κB, processes that are abolished in CSE deleted mice. As CSE deletion leads to decreased glutathione levels, resultant oxidative stress may contribute to alterations in CSE mutant mice. H2S acts by sulfhydrating the p65 subunit of NF-κB at cysteine-38, which promotes its binding to the co-activator ribosomal protein S3 (RPS3). Sulfhydration of p65 predominates early following TNFα treatment, then declines and is succeeded by a reciprocal enhancement of p65 nitrosylation. Anti-apoptotic influences of NF-κB, which are markedly diminished in CSE mutant mice. Thus, sulfhydration of NF-κB appears to be a physiologic determinant of its anti-apoptotic transcriptional activity.

Subfields: Biochemistry, Molecular Biology

View Paper: https://www.semanticscholar.org/paper/3fb6cd4e9c7cb588e7d49341e6aa324103366ed1

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Citations in the corpus

Hydrogen sulfide: a versatile regulator of environmental stress in plants (2015, background): “In addition, Sen et al. (2012) suggested that sulfhydration and nitrosylation both appear to regulate p65 subunit of nuclear factor jB and do so reciprocally.”
Reactive cysteine persulfides and S-polythiolation regulate oxidative stress and redox signaling (2014, neutral): “Others have shown that CSE activity can lead to persulfide formation, although this finding was mechanistically ill-defined (22), and another recent report alludes to polysulfide formation from H2S being responsible for signaling in the brain (23).”
Ribosomal proteins: functions beyond the ribosome. (2015, background): “Another example of RP involvement in immune signaling is RPS3 that selectively modulates NF-kB target gene expression.”