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Neuron. 2009 Jul 16;63(1):81-91. doi: 10.1016/j.neuron.2009.05.024.

GOSPEL: a neuroprotective protein that binds to GAPDH upon S-nitrosylation.

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  • 1Solomon H. Snyder Department of Neuroscience, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.

Erratum in

  • Neuron. 2009 Sep 10;63(5):709. Aggrawal, Nishant [corrected to Agrawal, Nishant].

Abstract

We recently reported a cell death cascade whereby cellular stressors activate nitric oxide formation leading to S-nitrosylation of GAPDH that binds to Siah and translocates to the nucleus. The nuclear GAPDH/Siah complex augments p300/CBP-associated acetylation of nuclear proteins, including p53, which mediate cell death. We report a 52 kDa cytosolic protein, GOSPEL, which physiologically binds GAPDH, in competition with Siah, retaining GAPDH in the cytosol and preventing its nuclear translocation. GOSPEL is neuroprotective, as its overexpression prevents NMDA-glutamate excitotoxicity while its depletion enhances death in primary neuron cultures. S-nitrosylation of GOSPEL at cysteine 47 enhances GAPDH-GOSPEL binding and the neuroprotective actions of GOSPEL. In intact mice, virally delivered GOSPEL selectively diminishes NMDA neurotoxicity. Thus, GOSPEL may physiologically regulate the viability of neurons and other cells.

Comment in

PMID:
19607794
[PubMed - indexed for MEDLINE]
PMCID:
PMC2758064
Free PMC Article

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