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Caspases and Cell Death

  1. Lorraine D Hernandez,
  2. Caroline Houde,
  3. Maarten Hoek,
  4. Brent Butts,
  5. Donald W Nicholson,
  6. Huseyin Mehmet

Published Online: 15 DEC 2009

DOI: 10.1002/9780470015902.a0021562

eLS

eLS

How to Cite

Hernandez, L. D., Houde, C., Hoek, M., Butts, B., Nicholson, D. W. and Mehmet, H. 2009. Caspases and Cell Death. eLS. .

Author Information

  1. Merck Research Laboratories, Rahway, New Jersey, USA

Publication History

  1. Published Online: 15 DEC 2009

Abstract

Caspases (Cysteinyl ASPartate-specific proteASE) are cysteine proteases involved in cell death. The caspase family is comprised of 12 proteins in humans, seven in Drosophila melanogaster and a single protein in Caenorhabditis elegans. All caspases consist of three structural domains: a prodomain, a large subunit and a small subunit. The catalytically active enzymes are formed either by proteolytic cleavage of the subunits, or through a proximity-induced activation process involving the prodomain. The cleavage site of caspase substrates is indicated by the positions P4, P3, P2 and P1. P1 is always aspartate, while amino acids in the other positions are highly variable. By cleaving over 1000 substrates in the cell, caspase activation results in the complete dismantling and ultimate death of the cell. Caspase activity can be regulated at a pharmacological level and has become a therapeutic target for the treatment of many diseases.

Key Concepts

  • Caspases (Cysteinyl ASPartate-specific proteASE) are the key enzymes regulating and executing apoptosis. They include several proteases acting either at the upstream regulatory events, or in the effector phase of cell death.

  • Three groups of caspases have been classified and are involved either in inflammation or cell death.

  • Caspases cleave over 1000 proteins within the cell causing the morphological events of cell death.

  • Both natural (cellular, bacterial and viral) and pharmacological inhibitors of caspases have been identified offering novel therapeutic approaches to inflammatory and apoptotic pathways.

Keywords:

  • apoptosis;
  • caspase;
  • cysteine protease;
  • cell death;
  • inflammation;
  • caspase inhibitor