| First Author | Sen N | Year | 2012 |
| Journal | Mol Cell | Volume | 45 |
| Issue | 1 | Pages | 13-24 |
| PubMed ID | 22244329 | Mgi Jnum | J:179897 |
| Mgi Id | MGI:5304595 | Doi | 10.1016/j.molcel.2011.10.021 |
| Citation | Sen N, et al. (2012) Hydrogen Sulfide-Linked Sulfhydration of NF-kappaB Mediates Its Antiapoptotic Actions. Mol Cell 45(1):13-24 |
| abstractText | Nuclear factor kappaB (NF-kappaB) is an antiapoptotic transcription factor. We show that the antiapoptotic actions of NF-kappaB are mediated by hydrogen sulfide (H(2)S) synthesized by cystathionine gamma-lyase (CSE). TNF-alpha treatment triples H(2)S generation by stimulating binding of SP1 to the CSE promoter. H(2)S generated by CSE stimulates DNA binding and gene activation of NF-kappaB, 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. H(2)S acts by sulfhydrating the p65 subunit of NF-kappaB at cysteine-38, which promotes its binding to the coactivator ribosomal protein S3 (RPS3). Sulfhydration of p65 predominates early after TNF-alpha treatment, then declines and is succeeded by a reciprocal enhancement of p65 nitrosylation. In CSE mutant mice, antiapoptotic influences of NF-kappaB are markedly diminished. Thus, sulfhydration of NF-kappaB appears to be a physiologic determinant of its antiapoptotic transcriptional activity. |
