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首页> 外文期刊>Cellular Signalling >Differential regulation of apoptosis by caspase-mediated cleavage of phospholipase D isozymes
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Differential regulation of apoptosis by caspase-mediated cleavage of phospholipase D isozymes

机译：caspase介导的磷脂酶D同工酶裂解对细胞凋亡的差异调节

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摘要

Phospholipase D (PLD) has been implicated in survival and anti-apoptosis, but the molecular mechanism by which it responds to apoptotic stimuli is poorly unknown. Here, we demonstrate that cleavage of PLD isozymes as specific substrates of caspase differentially regulates apoptosis. PLD1 is cleaved at one internal site (DDVD545S) and PLD2 is cleaved at two or three sites (PTGD(13)ELD(16)S and DEVD28T) in the front of N-terminus. Cleavage of PLD was endogenously detected in post-mortem Alzheimer brain together with activated caspase-3, suggesting the physiological relevance. The cleavage of PLD1 but not PLD2 might act as an inactivating process since PLD1 but not PLD2 activity is significantly decreased during apoptosis, suggesting that differential cleavage of PLD isozymes could affect its enzymatic activity. Moreover, caspase-resistant mutant of PLD1 showed more potent anti-apoptotic capacity than that of wild type PLD1, whereas PLD2 maintained anti-apoptotic potency in spite of its cleavage during apoptosis. Moreover, PLD2 showed more potent anti-apoptotic effect than that of PLD1 in overexpression and knockdown experiments, suggesting that difference in anti-apoptotic potency between PLD1 and PLD2 might be due to its intrinsic protein property. Taken together, our results demonstrate that differential cleavage pattern of PLD isozymes by caspase might affect its enzymatic activity and anti-apoptotic function. (c) 2008 Elsevier Inc. All rights reserved.
机译：磷脂酶D（PLD）参与了生存和抗凋亡，但其对凋亡刺激的分子机制尚不清楚。在这里，我们证明PLD同工酶作为caspase的特定底物的裂解差异调节细胞凋亡。 PLD1在N端前面的一个内部位点（DDVD545S）切割，PLD2在两个或三个位点（PTGD（13）ELD（16）S和DEVD28T）切割。在死后的阿尔茨海默病脑中与激活的caspase-3一起在内源性检测到了PLD的裂解，这表明其生理相关性。 PLD1而不是PLD2的切割可能是一个失活过程，因为PLD1而不是PLD2的活性在凋亡过程中显着降低了，这表明PLD同工酶的差异切割可能会影响其酶活性。此外，PLD1的耐半胱天冬酶突变体比野生型PLD1表现出更强的抗凋亡能力，而PLD2尽管在凋亡过程中被切割，但仍保持了抗凋亡能力。此外，在过表达和敲除实验中，PLD2显示出比PLD1更强的抗凋亡作用，这表明PLD1和PLD2之间的抗凋亡能力的差异可能是由于其固有的蛋白质特性所致。综上所述，我们的结果表明，胱天蛋白酶对PLD同工酶的不同切割方式可能影响其酶活性和抗凋亡功能。 （c）2008 Elsevier Inc.保留所有权利。

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