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Calpain and cell death

M K Squier1, J J Cohen

  • 1Department of Immunology, University of Colorado Medical School.

Cell Death and Differentiation
|July 1, 1996
PubMed

Insights

This review explores the role of calpain, a calcium-dependent protease, in programmed cell death (apoptosis). Calpain acts in the later stages of apoptosis, contributing to the irreversible cell death process.

Area of Science:

  • Biochemistry
  • Cell Biology
  • Molecular Biology

Background:

  • Apoptosis, or programmed cell death, involves complex signaling pathways.
  • The precise biochemical mechanisms initiating and executing apoptosis remain incompletely understood.
  • Existing signaling pathways typically mediate reversible cellular events, contrasting with the irreversible nature of cell death.

Purpose of the Study:

  • To review the role of calpain, a cysteine protease, in the biochemical execution of apoptosis.
  • To explore how proteolysis, specifically by calpain, contributes to the irreversibility of programmed cell death.
  • To position calpain's function within the broader context of apoptosis signaling pathways.

Main Methods:

  • Literature review of studies investigating apoptosis and protease function.
  • Analysis of the biochemical properties of calpain and its distinction from ICE-family proteases.
  • Examination of experimental evidence implicating calpain in physiological apoptosis.

Main Results:

  • Calpain, a calcium-dependent neutral protease, belongs to the papain superfamily of cysteine proteases.
  • Calpain plays a critical role in several key examples of physiological apoptosis.
  • Calpain appears to function downstream of initial signaling events but upstream of the final common pathway in apoptosis.

Conclusions:

  • Proteolysis, mediated by calpains, is a key irreversible process in cellular metabolism relevant to apoptosis.
  • Calpain's distinct biochemical activity positions it as a crucial effector in the programmed cell death cascade.
  • Understanding calpain's role provides insight into the biochemical definition of apoptosis execution.

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