Identification and inhibition of the ICE/CED-3 protease necessary for mammalian apoptosis

@article{Nicholson1995IdentificationAI,
  title={Identification and inhibition of the ICE/CED-3 protease necessary for mammalian apoptosis},
  author={Donald W. Nicholson and Ambereen Ali and Nancy Ann Thornberry and John P. Vaillancourt and Connie K. Ding and Michel. Gallant and Yves Gareau and Patrick R. Griffin and Marc. Labelle and Yuri A. Lazebnik and Neil A. Munday and S M Raju and Mark E. Smulson and T T Yamin and Violeta L. Yu and Douglas K. Miller},
  journal={Nature},
  year={1995},
  volume={376},
  pages={37-43}
}
The protease responsible for the cleavage of poly(ADP-ribose) polymerase and necessary for apoptosis has been purified and characterized. This enzyme, named apopain, is composed of two subunits of relative molecular mass (Mr) 17K and 12K that are derived from a common proenzyme identified as CPP32. This proenzyme is related to interleukin-lβ-converting enzyme (ICE) and CED-3, the product of a gene required for programmed cell death in Caenorhabditis elegans. A potent peptide aldehyde inhibitor… Expand
The caspase family of cysteine proteases.
TLDR
It is now clear that at least some members of the caspase (ICE/CED-3) family, which at present includes ten homologues of human origin, are essential components of an evolutionarily conserved pathway of apoptosis. Expand
ICE/CED-3 proteasesin apoptosis.
  • M. Whyte
  • Biology, Medicine
  • Trends in cell biology
  • 1996
TLDR
How functional characterization of these ICE-like proteases and identification of their substrates is helping to elucidate the biochemical processes underlying the stereotyped morphology of apoptosis and to identify potential targets for therapy is discussed. Expand
ICE/CED3-like Proteases as Therapeutic Targets for the Control of Inappropriate Apoptosis
TLDR
Among a growing number of potential molecular targets for the control of human diseases where inappropriate apoptosis is prominent, ICE/CED-3-like proteases may be an attractive and tangible point for therapeutic intervention. Expand
Caspases: the executioners of apoptosis.
  • G. Cohen
  • Biology, Medicine
  • The Biochemical journal
  • 1997
TLDR
The importance of caspase prodomains in the regulation of apoptosis is further highlighted by the recognition of adapter molecules, such as RAIDD [receptor-interacting protein (RIP)-associated ICH-1/CED-3-homologous protein with a death domain]/CRADD (caspase and RIP adapter with death domain), which binds to the prodomain of cspase-2 and recruits it to the signalling complex. Expand
CPP32/Apopain Is a Key Interleukin 1 Converting Enzyme-like Protease Involved in Fas-mediated Apoptosis (*)
TLDR
It is concluded that CPP32/apopain is activated in Fas-induced apoptosis and cleaves poly(ADP-ribose) polymerase (PARP) with high efficiency and specificity. Expand
Requirement of an ICE-Like Protease for Induction of Apoptosis and Ceramide Generation by REAPER
TLDR
The intracellular RPR protein uses cell death signaling pathways similar to those used by the vertebrate transmembrane receptors Fas (CD95) and tumor necrosis factor receptor type 1. Expand
The apoptotic cysteine protease CPP32.
  • S. Kumar
  • Biology, Medicine
  • The international journal of biochemistry & cell biology
  • 1997
TLDR
Inhibitors of CPP32 and other ICE-like proteases are potent inhibitors of apoptosis and promise to be important therapeutic molecules for the treatment of diseases, such as neurodegenerative and autoimmune disorders, that arise from excessive ell death. Expand
The three-dimensional structure of apopain/CPP32, a key mediator of apoptosis
TLDR
The three-dimensional structure of a complex of the human CED-3 homologue CPP32/apopain with a potent tetrapeptide-aldehyde inhibitor is determined, finding that the protein resembles ICE in overall structure, but its S4 subsite is strikingly different in size and chemical composition. Expand
Apopain/CPP32 cleaves proteins that are essential for cellular repair: a fundamental principle of apoptotic death
TLDR
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. Expand
Role of Ced-3/ICE-family proteases in staurosporine-induced programmed cell death
TLDR
Z-Val-Ala-Asp-fluoromethylketone (zVAD-fmk), a cell-permeable, irreversible, tripeptide inhibitor of some of these proteases, suppresses STS-induced and (STS + CHX)-induced cell death in a wide variety of mammalian cell types, providing strong evidence that these are all bona fide examples of PCD. Expand
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References

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TLDR
A novel protease resembling ICE (prICE) that is active in a cell-free system that reproduces the morphological and biochemical events of apoptosis in the extracts including morphological changes, cleavage of PARP and production of an oligonucleosomal ladder. Expand
Requirement of an ICE/CED-3 protease for Fas/APO-1-mediated apoptosis
TLDR
It is reported here that Fas/APO-1-mediated apoptosis requires the activation of a new class of cysteine proteases, including interleukin-lβ-converting enzyme (ICE)8á[euro]-10, which are homologous to the product of the Caenorhabditis elegans cell-death gene ced-3 (refs 11, 12). Expand
Molecular Cloning and Pro-apoptotic Activity of ICErelII and ICErelIII, Members of the ICE/CED-3 Family of Cysteine Proteases (*)
TLDR
Cysteine proteases related to mammalian interleukin-1β-converting enzyme (ICE) and the nematode cell death abnormal ced-3 gene product and two novel members of this new family of ICE/CED-3-related proteases were cloned from human monocytic cells and may participate in proteolytic events culminating in the apoptotic death of human cells. Expand
Involvement of an ICE-like protease in Fas-mediated apoptosis
TLDR
The results suggest an involvement of an ICE-like protease in Fas-mediated apoptosis and TNF-induced cytotoxicity and a specific ICE inhibitor tetrapeptide (acetyl-Tyr-Val-Ala-Asp-chloromethylketone) that also prevents apoptosis induced by anti-Fas antibody. Expand
Specific proteolytic cleavage of poly(ADP-ribose) polymerase: an early marker of chemotherapy-induced apoptosis.
TLDR
The results suggest that proteolytic cleavage of pADPRp, in addition to being an early marker of chemotherapy-induced apoptosis, might reflect more widespread proteolysis that is a critical biochemical event early during the process of physiological cell death. Expand
Crystal structure of the cysteine protease interleukin-1β-converting enzyme: A (p20/p10)2 homodimer
TLDR
Conservation among members of the ICE/CED-3 family of the amino acids that form the active site region of ICE supports the hypothesis that they share functional similarities. Expand
A novel heterodimeric cysteine protease is required for interleukin-1βprocessing in monocytes
TLDR
Purification and cloning of the complementary DNA indicates that IL-lβ-converting enzyme is composed of two nonidentical subunits that are derived from a single proenzyme, possibly by autoproteolysis. Expand
Induction of apoptosis in fibroblasts by IL-1β-converting enzyme, a mammalian homolog of the C. elegans cell death gene ced-3
TLDR
The results suggest that ICE may function during mammalian development to cause programmed cell death. Expand
Ich-1, an Ice/ced-3-related gene, encodes both positive and negative regulators of programmed cell death
TLDR
Overexpression of IchL induces programmed cell death, suggesting that Ich-1 is also a mammalian programmed cellDeath gene, and overexposure of the Ich- 1S suppresses Rat-1 cell death induced by serum deprivation, which suggests that Ich -1 plays an important role in both positive and negative regulation of programmed celldeath in vertebrate animals. Expand
Induction of apoptosis by the mouse Nedd2 gene, which encodes a protein similar to the product of the Caenorhabditis elegans cell death gene ced-3 and the mammalian IL-1 beta-converting enzyme.
TLDR
Overexpression of Nedd2 in cultured fibroblast and neuroblastoma cells resulted in cell death by apoptosis, which was suppressed by the expression of the human bcl-2 gene, indicating that Nedd 2 is functionally similar to the ced-3 gene in C. elegans. Expand
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