Letter | Published:

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

Naturevolume 371pages346347 (1994) | Download Citation

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Abstract

RECENT studies suggest that pro teases of the inter leukin 1-β-con-verting enzyme (ICE)/ced-3 family are involved in initiating the active phase of apoptosis1–3. 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 apoptosis4. prICE cleaves the nuclear enzyme poly(ADP-ribose) polymerase (PARP) at a tetrapeptide sequence identical to one of two ICE sites in pro-inter leu kin-l-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.

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Affiliations

  1. Department of Cell Biology and Anatomy, Johns Hopkins School of Medicine, 725 North Wolfe Street, Baltimore, Maryland, 21205, USA

    • Y. A. Lazebnik
    •  & W. C. Earnshaw
  2. Department of Oncology, Johns Hopkins School of Medicine, 725 North Wolfe Street, Baltimore, Maryland, 21205, USA

    • S. H. Kaufmann
  3. Department of Pharmacology, Johns Hopkins School of Medicine, 725 North Wolfe Street, Baltimore, Maryland, 21205, USA

    • S. H. Kaufmann
  4. Poly(ADP-Ribose) Metabolism Group, Department of Molecular Endocrinology, Centre Hospitalier de I'Université Laval Research Center and Laval University, Sainte-Foy, Quebec, Canada, G1V 4G2

    • S. Desnoyers
    •  & G. G. Poirier

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https://doi.org/10.1038/371346a0

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