Journal
JOURNAL OF CELL BIOLOGY
Volume 199, Issue 1, Pages 65-76Publisher
ROCKEFELLER UNIV PRESS
DOI: 10.1083/jcb.201205015
Keywords
-
Categories
Funding
- Brain Research Center of the 21st Century Frontier Research Program [NI-1:22-2009-00-010-00]
- Ministry of Education, Science and Technology, Republic of Korea
Ask authors/readers for more resources
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 a novel neuroprotective function of B23 through regulation of the SIAH1-glyceraldehyde-3-phosphate dehydrogenase ( GAPDH) death cascade. B23 physiologically bound to both SIAH1 and GAPDH, disrupting the SIAH1-GAPDH complex in the nucleus in response to nitrosative stress. S-nitrosylation of B23 at cysteine 275 by trans-nitrosylation from GAPDH dramatically reduced the interaction between SIAH1 and GAPDH. S-nitrosylation of B23 enhanced B23-SIAH1 binding and mediated the neuroprotective actions of B23 by abrogating the E3 ligase activity of SIAH1. In mice, overexpression of B23 notably inhibited N-methyl-D-aspartate-mediated neurotoxicity, whereas expression of the C275S mutant, which is defective in binding to SIAH1, did not prevent neurotoxicity. Thus, B23 regulates neuronal survival by preventing SIAH1-GAPDH death signaling under stress-induced conditions in the brain.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available