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KMID : 0578320090280060559
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Molecules and Cells
2009 Volume.28 No. 6 p.559 ~ p.563
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Glyceraldehyde-3-phosphate, a glycolytic intermediate, plays a key role in controlling cell fate via inhibition of caspase activity
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Jang MI
Kang Hyo-Jin
Lee Sun-Young
Chung Sang-J.
Kang Sung-Hyun
Chi Seung-Wook
Cho Sa-Yeon
Lee Sang-Chul
Lee Chong-Kil
Park Byoung-Chul
Bae Kwang-Hee
Park Sung-Goo
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Abstract
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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.
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KEYWORD
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aldolase, apoptosis, caspase-3, GAPDH, glyceraldehyde-3-phosphate
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