Differential regulation of apoptosis by caspase-mediated cleavage of phospholipase D isozymes

Young Hoon Jang, Bong Hyun Ahn, Seung Namkoong, Young Myeong Kim, Jae Kwang Jin, Yong Sun Kim, Do Sik Min

Research output: Contribution to journalArticle

14 Citations (Scopus)

Abstract

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 (PTGD13ELD16S 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.

Original languageEnglish
Pages (from-to)2198-2207
Number of pages10
JournalCellular Signalling
Volume20
Issue number12
DOIs
Publication statusPublished - 2008 Dec 1

All Science Journal Classification (ASJC) codes

  • Cell Biology

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