Glyceraldehyde-3-phosphate, a glycolytic intermediate, plays a key role in controlling cell fate via inhibition of caspase activity.
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.
Jang
Mi
M
Medical Proteomics Research Center, Korea Research Institute of Bioscience and Biotechnology, Daejeon 305-806, Korea.
Kang
Hyo Jin
HJ
Lee
Sun Young
SY
Chung
Sang J
SJ
Kang
Sunghyun
S
Chi
Seung Wook
SW
Cho
Sayeon
S
Lee
Sang Chul
SC
Lee
Chong-Kil
CK
Park
Byoung Chul
BC
Bae
Kwang-Hee
KH
Park
Sung Goo
SG
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
D005986:Glyceraldehyde 3-Phosphate; D005987:Glyceraldehyde-3-Phosphate Dehydrogenases; D053148:Caspase 3; D005634:Fructose-Bisphosphate Aldolase