Caspases: the proteases of the apoptotic pathway

Oncogene. 1998 Dec 24;17(25):3237-45. doi: 10.1038/sj.onc.1202581.

Abstract

Apoptosis, a morphologically defined form of physiological cell death, is implemented by a death machinery whose executionary arm is a family of cysteine proteases called caspases. These death proteases are part of a proteolytic caspase cascade that is activated by diverse apoptotic stimuli from outside and inside of the cell. The cell death machinery is evolutionarily conserved and composed of caspases and their regulatory components that include activators and repressors. These key components of the death machinery are linked to signaling pathways that are activated by either ligation of death receptors expressed at the cell surface or intracellular death signals. Caspases are normally present in the cell as proenzymes that require limited proteolysis for activation of enzymatic activity. Recent studies suggest that the basic mechanism of caspase activation is conserved in evolution. Binding of initiator caspase precursors to activator molecules appears to promote procaspase oligomerization and autoactivation. Enzymatic activation of initiator caspases leads to proteolytic activation of downstream (effector) caspases and cleavage of a number of vital proteins, resulting in the orderly demise and removal of the cell.

Publication types

  • Research Support, U.S. Gov't, Non-P.H.S.
  • Research Support, U.S. Gov't, P.H.S.
  • Review

MeSH terms

  • Animals
  • Apoptosis*
  • Caspases / physiology*
  • Cytochrome c Group / physiology
  • Enzyme Activation / drug effects
  • Enzyme Activation / physiology
  • Humans
  • Proto-Oncogene Proteins c-bcl-2 / physiology
  • Signal Transduction / physiology
  • Substrate Specificity

Substances

  • Cytochrome c Group
  • Proto-Oncogene Proteins c-bcl-2
  • Caspases