Cleavage of poly(ADP-ribose) polymerase by a proteinase with properties like ICE

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

Research output: Contribution to journalArticle

2233 Citations (Scopus)

Abstract

Recent studies suggest that proteases of the interleukin 1-β-converting enzyme (ICE)/ced-3 family are involved in initiating the active phase of apoptosis. Here we identify a novel protease resembling ICE (prICE) that is active in a cell-free system that reproduces the morphological and biochemical events of apoptosis. prICE cleaves the nuclear enzyme poly(ADP-ribose) polymerase (PARP) at a tetrapeptide sequence identical to one of two ICE sites in pro-interleukin-1-β. However, prICE does not cleave purified pro-interleukin-1-β, and purified ICE does not cleave PARP, indicating that the two activities are distinct. Inhibition of prICE abolishes all manifestations of apoptosis in the extracts including morphological changes, cleavage of PARP and production of an oligonucleosomal ladder. These studies suggest that prICE might be pivotal in initiating the active phase of apoptosis in vitro and in intact cells.

Original languageEnglish (US)
Pages (from-to)346-347
Number of pages2
JournalNature
Volume371
Issue number6495
DOIs
StatePublished - Sep 22 1994
Externally publishedYes

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Caspase 1
Poly(ADP-ribose) Polymerases
Peptide Hydrolases
Apoptosis
Interleukin-1
Cell-Free System
protease resembling ICE
Enzymes

ASJC Scopus subject areas

  • General

Cite this

Lazebnik, Y. A., Kaufmann, S. H., Desnoyers, S., Poirier, G. G., & Earnshaw, W. C. (1994). Cleavage of poly(ADP-ribose) polymerase by a proteinase with properties like ICE. Nature, 371(6495), 346-347. https://doi.org/10.1038/371346a0

Cleavage of poly(ADP-ribose) polymerase by a proteinase with properties like ICE. / Lazebnik, Y. A.; Kaufmann, Scott H; Desnoyers, S.; Poirier, G. G.; Earnshaw, W. C.

In: Nature, Vol. 371, No. 6495, 22.09.1994, p. 346-347.

Research output: Contribution to journalArticle

Lazebnik, YA, Kaufmann, SH, Desnoyers, S, Poirier, GG & Earnshaw, WC 1994, 'Cleavage of poly(ADP-ribose) polymerase by a proteinase with properties like ICE', Nature, vol. 371, no. 6495, pp. 346-347. https://doi.org/10.1038/371346a0
Lazebnik, Y. A. ; Kaufmann, Scott H ; Desnoyers, S. ; Poirier, G. G. ; Earnshaw, W. C. / Cleavage of poly(ADP-ribose) polymerase by a proteinase with properties like ICE. In: Nature. 1994 ; Vol. 371, No. 6495. pp. 346-347.
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