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

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 delivere

SUBMITTER: Sen N 

PROVIDER: S-EPMC2758064 | biostudies-literature | 2009 Jul

REPOSITORIES: biostudies-literature