RGD Reference Report - GOSPEL: a neuroprotective protein that binds to GAPDH upon S-nitrosylation. - Rat Genome Database

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

Authors: Sen, N  Hara, MR  Ahmad, AS  Cascio, MB  Kamiya, A  Ehmsen, JT  Agrawal, N  Hester, L  Dore, S  Snyder, SH  Sawa, A 
Citation: Sen N, etal., Neuron. 2009 Jul 16;63(1):81-91. doi: 10.1016/j.neuron.2009.05.024.
RGD ID: 8553565
Pubmed: PMID:19607794   (View Abstract at PubMed)
PMCID: PMC2758064   (View Article at PubMed Central)
DOI: DOI:10.1016/j.neuron.2009.05.024   (Journal Full-text)

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.

Gene Ontology Annotations    Click to see Annotation Detail View

Biological Process
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
nitric oxide mediated signal transduction involved_inIDA 8553565; 8553565PMID:19607794UniProt 

Cellular Component
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
cytosol located_inIDA 8553565; 8553565PMID:19607794UniProt 
nucleus located_inIDA 8553565PMID:19607794UniProt 

Molecular Function
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
protein binding enablesIPIUniProtKB:D3ZUQ08553565PMID:19607794UniProt 
protein binding enablesIPIUniProtKB:Q920M98553565PMID:19607794UniProt 
protein binding enablesIPIUniProtKB:P047978553565; 8553565PMID:19607794UniProt 

Objects Annotated

Genes (Rattus norvegicus)
Gapdh  (glyceraldehyde-3-phosphate dehydrogenase)
Rilpl1  (Rab interacting lysosomal protein-like 1)
Siah1  (siah E3 ubiquitin protein ligase 1)


Additional Information