S-nitrosylation of B23/nucleophosmin by GAPDH protects cells from the SIAH1–GAPDH death cascade

• DOI: 10.1083/jcb.201205015
• Publication Date: 2012-10-01T17:45:17Z
• Authors: Sang Bae Lee; Chung Kwon Kim; Kyung-Hoon Lee; Jee-Yin Ahn
• Keywords: Nucleophosmin; Glyceraldehyde 3-phosphate dehydrogenase; S-Nitrosylation; Nitrosylation

B23/nucleophosmin is a multifunctional protein that participates in cell survival signaling by shuttling between the nucleolus/nucleoplasm and nucleus/cytoplasm. In this paper, we report novel neuroprotective function of B23 through regulation SIAH1–glyceraldehyde-3-phosphate dehydrogenase (GAPDH) death cascade. physiologically bound to both SIAH1 GAPDH, disrupting SIAH1–GAPDH complex nucleus response nitrosative stress. S-nitrosylation at cysteine 275 trans-nitrosylation from GAPDH dramatically reduced interaction GAPDH. enhanced B23–SIAH1 binding mediated actions abrogating E3 ligase activity SIAH1. mice, overexpression notably inhibited N-methyl-d-aspartate–mediated neurotoxicity, whereas expression C275S mutant, which defective SIAH1, did not prevent neurotoxicity. Thus, regulates neuronal preventing under stress-induced conditions brain.