Cleavage of phospholipase D1 by caspase promotes apoptosis via modulation of the p53-dependent cell death pathway

Y. H. Jang, S. Namkoong, Y. M. Kim, S. J. Lee, B. J. Park, D. S. Min

Research output: Contribution to journalArticle

12 Citations (Scopus)

Abstract

The enzymatic activity of phospholipase D (PLD) is known to be essential for cell survival and protection from apoptosis. However, the mechanisms regulating PLD activity during apoptosis remain unknown. Here we report that cleavage of PLD1 by caspases facilitates p53-mediated apoptosis. Cleavage of PLD1 into an N-terminal fragment (NF-PLD1) and a C-terminal fragment at the amino-acid sequence, DDVD545, led to a reduction in PLD1 activity. However, a caspase-resistant mutant form of PLD1 retained significant levels of enzymatic activity and apoptotic function as compared to wild-type PLD1. Exogenous NF-PLD1 expression induced apoptosis through a dominant-negative effect on the activity of endogenous PLD1. During apoptosis, a small fraction of PLD1 is cleaved by caspases in a p53-independent manner and NF-PLD1 amplifies apoptotic signaling through inhibition of the remaining PLD1 activity. As PLD1 suppresses the ATM-Chk2-p53 pathway, elimination of PLD1 activity through NF-PLD1 or si-RNA against PLD1 increases apoptosis in a p53-dependent manner. Taken together, our results reveal that cleavage of PLD1 by caspases promotes apoptosis via modulation of the p53-dependent cell death pathway.

Original languageEnglish
Pages (from-to)1782-1793
Number of pages12
JournalCell Death and Differentiation
Volume15
Issue number11
DOIs
Publication statusPublished - 2008 Jul 21

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Caspases
Cell Death
Apoptosis
Phospholipase D
Cytoprotection
phospholipase D1
Amino Acid Sequence
Cell Survival
RNA

All Science Journal Classification (ASJC) codes

  • Molecular Biology
  • Cell Biology

Cite this

Jang, Y. H. ; Namkoong, S. ; Kim, Y. M. ; Lee, S. J. ; Park, B. J. ; Min, D. S. / Cleavage of phospholipase D1 by caspase promotes apoptosis via modulation of the p53-dependent cell death pathway. In: Cell Death and Differentiation. 2008 ; Vol. 15, No. 11. pp. 1782-1793.
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Cleavage of phospholipase D1 by caspase promotes apoptosis via modulation of the p53-dependent cell death pathway. / Jang, Y. H.; Namkoong, S.; Kim, Y. M.; Lee, S. J.; Park, B. J.; Min, D. S.

In: Cell Death and Differentiation, Vol. 15, No. 11, 21.07.2008, p. 1782-1793.

Research output: Contribution to journalArticle

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