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.
journal_name
Cell Repjournal_title
Cell reportsauthors
Okamoto S,Nakamura T,Cieplak P,Chan SF,Kalashnikova E,Liao L,Saleem S,Han X,Clemente A,Nutter A,Sances S,Brechtel C,Haus D,Haun F,Sanz-Blasco S,Huang X,Li H,Zaremba JD,Cui J,Gu Z,Nikzad R,Harrop A,McKercher SRdoi
10.1016/j.celrep.2014.06.005subject
Has Abstractpub_date
2014-07-10 00:00:00pages
217-28issue
1issn
2211-1247pii
S2211-1247(14)00455-0journal_volume
8pub_type
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