GOSPEL

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

Nilkantha Sen, Makoto R. Hara, Abdullah Shafique Ahmad, Matthew B. Cascio, Atsushi Kamiya, Jeffrey T. Ehmsen, Nishant Aggrawal, Lynda Hester, Sylvain Doré, Solomon H. Snyder, Akira Sawa

Research output: Contribution to journalArticle

93 Citations (Scopus)

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.

Original languageEnglish (US)
Pages (from-to)81-91
Number of pages11
JournalNeuron
Volume63
Issue number1
StatePublished - Jul 16 2009

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N-Methylaspartate
Cell Death
Neurons
Acetylation
Nuclear Proteins
Cytosol
Cysteine
Glutamic Acid
Nitric Oxide
Proteins

ASJC Scopus subject areas

  • Neuroscience(all)

Cite this

Sen, N., Hara, M. R., Ahmad, A. S., Cascio, M. B., Kamiya, A., Ehmsen, J. T., ... Sawa, A. (2009). GOSPEL: a neuroprotective protein that binds to GAPDH upon S-nitrosylation. Neuron, 63(1), 81-91.

GOSPEL : a neuroprotective protein that binds to GAPDH upon S-nitrosylation. / Sen, Nilkantha; Hara, Makoto R.; Ahmad, Abdullah Shafique; Cascio, Matthew B.; Kamiya, Atsushi; Ehmsen, Jeffrey T.; Aggrawal, Nishant; Hester, Lynda; Doré, Sylvain; Snyder, Solomon H.; Sawa, Akira.

In: Neuron, Vol. 63, No. 1, 16.07.2009, p. 81-91.

Research output: Contribution to journalArticle

Sen, N, Hara, MR, Ahmad, AS, Cascio, MB, Kamiya, A, Ehmsen, JT, Aggrawal, N, Hester, L, Doré, S, Snyder, SH & Sawa, A 2009, 'GOSPEL: a neuroprotective protein that binds to GAPDH upon S-nitrosylation.', Neuron, vol. 63, no. 1, pp. 81-91.
Sen N, Hara MR, Ahmad AS, Cascio MB, Kamiya A, Ehmsen JT et al. GOSPEL: a neuroprotective protein that binds to GAPDH upon S-nitrosylation. Neuron. 2009 Jul 16;63(1):81-91.
Sen, Nilkantha ; Hara, Makoto R. ; Ahmad, Abdullah Shafique ; Cascio, Matthew B. ; Kamiya, Atsushi ; Ehmsen, Jeffrey T. ; Aggrawal, Nishant ; Hester, Lynda ; Doré, Sylvain ; Snyder, Solomon H. ; Sawa, Akira. / GOSPEL : a neuroprotective protein that binds to GAPDH upon S-nitrosylation. In: Neuron. 2009 ; Vol. 63, No. 1. pp. 81-91.
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AU - Ehmsen, Jeffrey T.

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