Apopain/CPP32 cleaves proteins that are essential for cellular repair: A fundamental principle of apoptotic death

Livia Casciola-Rosen, Donald W. Nicholson, Tae Chong, Kevin R. Rowan, Nancy A. Thornberry, Douglas K. Miller, Antony Rosen

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577 Scopus citations


Proteolysis mediated by the interleukin 1β-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-PK(cs)). The present studies demonstrate that U1-70kD and DNA-PK(cs) 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.

Original languageEnglish (US)
Pages (from-to)1957-1964
Number of pages8
JournalJournal of Experimental Medicine
Issue number5
StatePublished - May 1 1996

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology


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