PMID- 22534308 OWN - NLM STAT- MEDLINE DCOM- 20120820 LR - 20190923 IS - 1738-8872 (Electronic) IS - 1017-7825 (Linking) VI - 22 IP - 4 DP - 2012 Apr TI - Glyceraldehyde-3-phosphate, a glycolytic intermediate, prevents cells from apoptosis by lowering S-nitrosylation of glyceraldehyde-3-phosphate dehydrogenase. PG - 571-3 AB - 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. FAU - Lee, Sun Young AU - Lee SY AD - Medical Proteomics Research Center, KRIBB, Daejeon 305-806, Korea. FAU - Kim, Jeong Hoon AU - Kim JH FAU - Jung, Hyeyun AU - Jung H FAU - Chi, Seung Wook AU - Chi SW FAU - Chung, Sang J AU - Chung SJ FAU - Lee, Chong-Kil AU - Lee CK FAU - Park, Byoung Chul AU - Park BC FAU - Bae, Kwang-Hee AU - Bae KH FAU - Park, Sung Goo AU - Park SG LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't PL - Korea (South) TA - J Microbiol Biotechnol JT - Journal of microbiology and biotechnology JID - 9431852 RN - 142-10-9 (Glyceraldehyde 3-Phosphate) RN - EC 1.2.1.- (Glyceraldehyde-3-Phosphate Dehydrogenases) RN - EC 3.4.22.- (Caspase 3) SB - IM MH - *Apoptosis MH - Caspase 3/metabolism MH - Cells/*cytology/enzymology/metabolism MH - Glyceraldehyde 3-Phosphate/*metabolism MH - Glyceraldehyde-3-Phosphate Dehydrogenases/*metabolism MH - HeLa Cells MH - Humans EDAT- 2012/04/27 06:00 MHDA- 2012/08/21 06:00 CRDT- 2012/04/27 06:00 PHST- 2012/04/27 06:00 [entrez] PHST- 2012/04/27 06:00 [pubmed] PHST- 2012/08/21 06:00 [medline] AID - JMB022-04-20 [pii] AID - 10.4014/jmb.1110.10010 [doi] PST - ppublish SO - J Microbiol Biotechnol. 2012 Apr;22(4):571-3. doi: 10.4014/jmb.1110.10010.