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KMID : 0545120120220040571
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Journal of Microbiology and Biotechnology
2012 Volume.22 No. 4 p.571 ~ p.573
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Glyceraldehyde-3-Phosphate, a Glycolytic Intermediate, Prevents Cells from Apoptosis by Lowering S-Nitrosylation of Glyceraldehyde-3-Phosphate Dehydrogenase
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Lee Sun-Young
Kim Jeong-Hoon
Jung Hyeyun
Chi Seung-Wook
Chung Sang-J.
Lee Chong-Kil
Park Byoung-Chul
Bae Kwang-Hee
Park Sung-Goo
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Abstract
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Glyceraldehyde-3-phosphate (G-3-P), the substrate of glyceraldehyde-3-phosphate dehydrogenase (GAPDH), is a key intermediate in several metabolic pathways. Recently, we reported that G-3-P directly inhibits caspase-3 activity in a reversible noncompetitive mode, suggesting the intracellular G-3-P level as a cell fate decision factor. It has been known that apoptotic stimuli induce the generation of NO, and NO S-nitrosylates GAPDH at the catalytic cysteine residue, which confers GAPDH the ability to bind to Siah-1, an E3 ubiquitin ligase. The GAPDH-Siah-1 complex is translocated into the nucleus and subsequently triggers the apoptotic process. Here, we clearly showed that intracellular G-3-P protects GAPDH from S-nitrosylation at above a certain level, and consequently maintains the cell survival. In case G-3-P drops below a certain level as a result of exposure to specific stimuli, G-3-P cannot inhibit S-nitrosylation of GAPDH anymore, and consequently GAPDH translocates with Siah-1 into the nucleus. Based on these results, we suggest that G-3-P functions as a molecule switch between cell survival and apoptosis by regulating S-nitrosylation of GAPDH.
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KEYWORD
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Apoptosis, GAPDH, Glyceraldehyde-3-phosphate, S-nitrosylation
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