title: Glyceraldehyde-3-phosphate, a glycolytic intermediate, prevents cells from apoptosis by lowering S-nitrosylation of glyceraldehyde-3-phosphate dehydrogenase.
abstract: 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.
authors.affiliation: Medical Proteomics Research Center, KRIBB, Daejeon 305-806, Korea.
authors.forename: Sun Young
authors.initials: SY
authors.lastname: Lee
authors.forename: Jeong Hoon
authors.initials: JH
authors.lastname: Kim
authors.forename: Hyeyun
authors.initials: H
authors.lastname: Jung
authors.forename: Seung Wook
authors.initials: SW
authors.lastname: Chi
authors.forename: Sang J
authors.initials: SJ
authors.lastname: Chung
authors.forename: Chong-Kil
authors.initials: CK
authors.lastname: Lee
authors.forename: Byoung Chul
authors.initials: BC
authors.lastname: Park
authors.forename: Kwang-Hee
authors.initials: KH
authors.lastname: Bae
authors.forename: Sung Goo
authors.initials: SG
authors.lastname: Park
mesh_terms: D017209:Apoptosis; D053148:Caspase 3 / Q000378:metabolism; D002477:Cells / Q000166:cytology* / Q000201:enzymology / Q000378:metabolism; D005986:Glyceraldehyde 3-Phosphate / Q000378:metabolism*; D005987:Glyceraldehyde-3-Phosphate Dehydrogenases / Q000378:metabolism*; D006367:HeLa Cells; D006801:Humans
chemical_list: D005986:Glyceraldehyde 3-Phosphate; D005987:Glyceraldehyde-3-Phosphate Dehydrogenases; D053148:Caspase 3