| First Author | Sen N | Year | 2009 |
| Journal | Neuron | Volume | 63 |
| Issue | 1 | Pages | 81-91 |
| PubMed ID | 19607794 | Mgi Jnum | J:154950 |
| Mgi Id | MGI:4411968 | Doi | 10.1016/j.neuron.2009.05.024 |
| Citation | Sen N, et al. (2009) GOSPEL: a neuroprotective protein that binds to GAPDH upon S-nitrosylation. Neuron 63(1):81-91 |
| abstractText | 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. |
