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(NAS Colloquium) Proteolytic Processing and Physiological Regulation (1999) / Chapter Skim
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Caspase activation: The induced-proximity model
Pages 10964-10967

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From page 10964...
... DIXITT * Programs in Cell Death and Aging Research, Burnham Institute, 10901 North Torrey Pines Road, La Jolla, CA 92037; and Department of Molecular Oncology, Genentech Inc., 460 Point San Bruno Boulevard, South San Francisco, CA 94080 ABSTRACT Members of the caspase family of proteases specific ligands, these receptors transmit a lethal signal that transmit the events that lead to apoptosis of animal cells.
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From page 10965...
... Significantly, the frozen zymogen retained the same specificity against caspase inhibitors and synthetic substrates but cleaved these substrates at 1% of the rate of an equivalent concentration of fully processed enzyme. The mechanistic origin of this rate differential is currently unknown, but, significantly, the zymogenicity of caspase-8, the ratio of its activity as a fully active enzyme to the activity of its unprocessed zymogen, was 100 (4~.
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From page 10966...
... answerable by generating specific mutants and by using the artificial death-switch technique. Perhaps it is already possible to settle the issue of cis versus bans processing; in our hands, it is rarely possible to observe activation of caspase zymogens in the nanomolar range, but on artificial concentration toward the micromolar range, one observes processing and activation.
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From page 10967...
... Cell Biol.
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Key Terms

  • cell death
  • death receptors
  • executioner caspases
  • numbering convention
  • proteolytic processing

  • substrate specificity
  • initiator caspases
  • signaling complexes
  • intrinsic proteolytic
  • active form

  • proteolytic activity
  • activation usually
  • limited proteolysis
  • signaling complex
  • tumor necrosis

  • caspase inhibitors
  • unprocessed zymogen
  • active caspases
  • death signals
  • proteolytic signal

  • enzymatic activity
  • active caspase
  • caspase family
  • human cell
  • adjacent zymogen

  • torrey pines
  • held february
  • specificity determinants
  • cognate ligand
  • readily explained


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