| First Author | Okamoto S | Year | 2014 |
| Journal | Cell Rep | Volume | 8 |
| Issue | 1 | Pages | 217-28 |
| PubMed ID | 25001280 | Mgi Jnum | J:212072 |
| Mgi Id | MGI:5578047 | Doi | 10.1016/j.celrep.2014.06.005 |
| Citation | Okamoto S, et al. (2014) S-nitrosylation-mediated redox transcriptional switch modulates neurogenesis and neuronal cell death. Cell Rep 8(1):217-28 |
| abstractText | Redox-mediated posttranslational modifications represent a molecular switch that controls major mechanisms of cell function. Nitric oxide (NO) can mediate redox reactions via S-nitrosylation, representing transfer of an NO group to a critical protein thiol. NO is known to modulate neurogenesis and neuronal survival in various brain regions in disparate neurodegenerative conditions. However, a unifying molecular mechanism linking these phenomena remains unknown. Here, we report that S-nitrosylation of myocyte enhancer factor 2 (MEF2) transcription factors acts as a redox switch to inhibit both neurogenesis and neuronal survival. Structure-based analysis reveals that MEF2 dimerization creates a pocket, facilitating S-nitrosylation at an evolutionally conserved cysteine residue in the DNA binding domain. S-Nitrosylation disrupts MEF2-DNA binding and transcriptional activity, leading to impaired neurogenesis and survival in vitro and in vivo. Our data define a molecular switch whereby redox-mediated posttranslational modification controls both neurogenesis and neurodegeneration via a single transcriptional signaling cascade. |
