alexa S-nitrosylation-mediated redox transcriptional switch modulates neurogenesis and neuronal cell death.
Immunology

Immunology

Journal of Cell Signaling

Author(s): Okamoto S, Nakamura T, Cieplak P, Chan SF, Kalashnikova E,

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Abstract 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. Copyright © 2014 The Authors. Published by Elsevier Inc. All rights reserved.
This article was published in Cell Rep and referenced in Journal of Cell Signaling

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