Characterization of the execution phase of apoptosis in vitro using extracts from condemned-phase cells

Y. A. Lazebnik, A. Takahashi, G. G. Poirier, S. H. Kaufmann, W. C. Earnshaw

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45 Scopus citations

Abstract

Apoptotic cell death is characterized by a dramatic morphological transformation during which apparently healthy cells suddenly initiate a comprehensive program of motility changes and degradative activities that culminates in disassembly of the cell into membrane-enclosed vesicles. The mechanism of the cellular changes during this spectacular execution phase of apoptosis is just now yielding to biochemical analysis. In our laboratory, we have applied a novel in vitro system to the study of these events. In this system, nuclei isolated from healthy cells undergo the characteristic changes of apoptosis rapidly and synchronously. Using this system we have identified the first substrates for interleukin-1β-converting enzyme (ICE)-like proteinases during apoptotic execution. One of these, the nuclear enzyme poly (ADP-ribose) polymerase is cleaved very early in the apoptotic process. A second class of proteins, the nuclear lamins, is cleaved later in the pathway. Lamin cleavage requires a second ICE-related proteinase, and is essential for the complete dissolution of nuclei into apoptotic bodies. Studies with our cell-free extracts reveal that the various proteinases and nucleases that operate during the execution phase of apoptosis do so largely in independent parallel biochemical pathways. However, all of these pathways require the action of ICE-related proteinases for their initiation.

Original languageEnglish (US)
Pages (from-to)41-49
Number of pages9
JournalJournal of cell science
Volume108
Issue numberSUPPL. 19
StatePublished - Jan 1 1995

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Keywords

  • Apoptosis
  • ICE-like proteinase
  • Nuclear lamin
  • Nucleus
  • Transformation

ASJC Scopus subject areas

  • Cell Biology

Cite this

Lazebnik, Y. A., Takahashi, A., Poirier, G. G., Kaufmann, S. H., & Earnshaw, W. C. (1995). Characterization of the execution phase of apoptosis in vitro using extracts from condemned-phase cells. Journal of cell science, 108(SUPPL. 19), 41-49.