Proteolysis mediated by the interleukin 1 beta-converting enzyme (ICE) homologues is an important mechanism of the apoptotic process. The ICE homologue apopain/CPP-32/Yama (subsequently referred to as apopain) cleaves poly(ADP-ribose)polymerase (PARP) early during apoptosis. Additional apoptosis-specific protein cleavages have been observed in which the direct involvement of ICE-like proteases has been postulated. These substrates include the 70-kD protein component of the U1-ribonucleoprotein (U1-70kD), and the catalytic subunit of the DNA-dependent protein kinase (DNA-PKcs). The present studies demonstrate that U1-70kD and DNA-PKcs are excellent substrates for apopain, with cleavage occurring at sites that are highly similar to the cleavage site within PARP. The fragments generated from isolated protein substrates by apopain are identical to those observed in intact apoptotic cells, in apoptotic cell extracts, and in normal cell extracts to which apopain has been added. Like PARP, cleavage of these substrates in apoptotic cell extracts is abolished by nanomolar concentrations of Ac-DEVD-CHO and micromolar amounts of Ac-YVAD-CHO, confirming the involvement of apopain or an apopain-like activity. We propose that a central function of apopain or similar homologues in apoptosis is the cleavage of nuclear repair proteins, thereby abolishing their critical homeostatic functions.
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May 01 1996
Apopain/CPP32 cleaves proteins that are essential for cellular repair: a fundamental principle of apoptotic death.
L Casciola-Rosen,
L Casciola-Rosen
Department of Dermatology, Johns Hopkins University School of Medicine, Baltimore, Maryland 21205, USA.
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D W Nicholson,
D W Nicholson
Department of Dermatology, Johns Hopkins University School of Medicine, Baltimore, Maryland 21205, USA.
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T Chong,
T Chong
Department of Dermatology, Johns Hopkins University School of Medicine, Baltimore, Maryland 21205, USA.
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K R Rowan,
K R Rowan
Department of Dermatology, Johns Hopkins University School of Medicine, Baltimore, Maryland 21205, USA.
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N A Thornberry,
N A Thornberry
Department of Dermatology, Johns Hopkins University School of Medicine, Baltimore, Maryland 21205, USA.
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D K Miller,
D K Miller
Department of Dermatology, Johns Hopkins University School of Medicine, Baltimore, Maryland 21205, USA.
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A Rosen
A Rosen
Department of Dermatology, Johns Hopkins University School of Medicine, Baltimore, Maryland 21205, USA.
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L Casciola-Rosen
Department of Dermatology, Johns Hopkins University School of Medicine, Baltimore, Maryland 21205, USA.
D W Nicholson
Department of Dermatology, Johns Hopkins University School of Medicine, Baltimore, Maryland 21205, USA.
T Chong
Department of Dermatology, Johns Hopkins University School of Medicine, Baltimore, Maryland 21205, USA.
K R Rowan
Department of Dermatology, Johns Hopkins University School of Medicine, Baltimore, Maryland 21205, USA.
N A Thornberry
Department of Dermatology, Johns Hopkins University School of Medicine, Baltimore, Maryland 21205, USA.
D K Miller
Department of Dermatology, Johns Hopkins University School of Medicine, Baltimore, Maryland 21205, USA.
A Rosen
Department of Dermatology, Johns Hopkins University School of Medicine, Baltimore, Maryland 21205, USA.
Online ISSN: 1540-9538
Print ISSN: 0022-1007
J Exp Med (1996) 183 (5): 1957–1964.
Citation
L Casciola-Rosen, D W Nicholson, T Chong, K R Rowan, N A Thornberry, D K Miller, A Rosen; Apopain/CPP32 cleaves proteins that are essential for cellular repair: a fundamental principle of apoptotic death.. J Exp Med 1 May 1996; 183 (5): 1957–1964. doi: https://doi.org/10.1084/jem.183.5.1957
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