Journal
CELL REPORTS
Volume 8, Issue 1, Pages 217-228Publisher
CELL PRESS
DOI: 10.1016/j.celrep.2014.06.005
Keywords
-
Categories
Funding
- Japan Society for Promotion of Science
- California HIV/AIDS Research Program, a Shiley-Marcos Alzheimer's Disease Research Center (UCSD) Pilot Award, NIH [R21 MH102672]
- NIH [P01 HD29587, P01 ES016738, P30 NS076411]
Ask authors/readers for more resources
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.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available