title: Glyceraldehyde-3-phosphate, a glycolytic intermediate, plays a key role in controlling cell fate via inhibition of caspase activity.
abstract: Glyceraldehyde-3-phosphate is a key intermediate in several central metabolic pathways of all organisms. Aldolase and glyceraldehyde-3-phosphate dehydrogenase are involved in the production or elimination of glyceraldehyde-3-phosphate during glycolysis or gluconeogenesis, and are differentially expressed under various physiological conditions, including cancer, hypoxia, and apoptosis. In this study, we examine the effects of glyceraldehyde-3-phosphate on cell survival and apoptosis. Overexpression of aldolase protected cells against apoptosis, and addition of glyceraldehyde-3-phosphate to cells delayed apoptosis. Additionally, delayed apoptotic phenomena were observed when glyceraldehyde-3-phosphate was added to a cell-free system, in which artificial apoptotic process was induced by adding dATP and cytochrome c. Surprisingly, glyceraldehyde-3-phosphate directly suppressed caspase-3 activity in a reversible noncompetitive mode, preventing caspase-dependent proteolysis. Based on these results, we suggest that glyceraldehyde-3-phosphate, a key molecule in several central metabolic pathways, functions as a molecule switch between cell survival and apoptosis.
authors: Medical Proteomics Research Center, Korea Research Institute of Bioscience and Biotechnology, Daejeon 305-806, Korea.
authors: Mi
authors: M
authors: Jang
authors: Hyo Jin
authors: HJ
authors: Kang
authors: Sun Young
authors: SY
authors: Lee
authors: Sang J
authors: SJ
authors: Chung
authors: Sunghyun
authors: S
authors: Kang
authors: Seung Wook
authors: SW
authors: Chi
authors: Sayeon
authors: S
authors: Cho
authors: Sang Chul
authors: SC
authors: Lee
authors: Chong-Kil
authors: CK
authors: Lee
authors: Byoung Chul
authors: BC
authors: Park
authors: Kwang-Hee
authors: KH
authors: Bae
authors: Sung Goo
authors: SG
authors: Park
mesh_terms: D017209:Apoptosis / Q000187:drug effects* / Q000235:genetics; D053148:Caspase 3 / Q000235:genetics / Q000378:metabolism*; D002470:Cell Survival / Q000187:drug effects* / Q000235:genetics; D005634:Fructose-Bisphosphate Aldolase / Q000235:genetics / Q000378:metabolism; D015971:Gene Expression Regulation, Enzymologic; D005986:Glyceraldehyde 3-Phosphate / Q000494:pharmacology*; D005987:Glyceraldehyde-3-Phosphate Dehydrogenases / Q000235:genetics / Q000378:metabolism; D006019:Glycolysis; D018922:HL-60 Cells; D006801:Humans; D007962:Leukocytes / Q000187:drug effects* / Q000201:enzymology / Q000276:immunology / Q000473:pathology; D014162:Transfection
chemical_list: D005986:Glyceraldehyde 3-Phosphate; D005987:Glyceraldehyde-3-Phosphate Dehydrogenases; D053148:Caspase 3; D005634:Fructose-Bisphosphate Aldolase