A mathematical model of caspase function in apoptosis

  title={A mathematical model of caspase function in apoptosis},
  author={Martin Fussenegger and James Edwin Bailey and Jeffrey D. Varner},
  journal={Nature Biotechnology},
Caspases (cysteine-containing aspartate-specific proteases) are at the core of the cell's suicide machinery. These enzymes, once activated, dismantle the cell by selectively cleaving key proteins after aspartate residues. The events culminating in caspase activation are the subject of intense study because of their role in cancer, and neurodegenerative and autoimmune disorders. Here we present a mechanistic mathematical model, formulated on the basis of newly emerging information, describing… 
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  • G. Salvesen, V. Dixit
  • Biology
    Proceedings of the National Academy of Sciences of the United States of America
  • 1999
Evidence for a hypothesis-the induced-proximity model-that describes how the first proteolytic signal is produced after adapter-mediated clustering of initiator caspase zymogens is reviewed.
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It is shown that human X-chromosome-linked IAP directly inhibits at least two members of the caspase family of cell-death proteases, caspasing-3 and caspases-7, providing evidence for a mechanism of action for these mammalian cell- death suppressors.
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Two studies show that symptoms of Huntington's disease are less severe when caspase-1-mediated cleavage of the huntingtin protein is blocked and the cytoplasmic domain of the beta-amyloid precursor protein is shown to be cleaved directly by caspases, leading to increased production of the amyloid-beta peptide.
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Bcl-2 and related cytoplasmic proteins are key regulators of apoptosis, the cell suicide program critical for development, tissue homeostasis, and protection against pathogens. Those most similar to
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This work has shown that understanding caspase regulation is intimately linked to the ability to rationally manipulate apoptosis for therapeutic gain.