Mammalian caspases

Structure, activation, substrates, and functions during apoptosis

William C. Earnshaw, Luis M. Martins, Scott H Kaufmann

Research output: Contribution to journalArticle

2297 Citations (Scopus)

Abstract

Apoptosis is a genetically programmed, morphologically distinct form of cell death that can be triggered by a variety of physiological and pathological stimuli. Studies performed over the past 10 years have demonstrated that proteases play critical roles in initiation and execution of this process. The caspases, a family of cysteine-dependent aspartate- directed proteases, are prominent among the death proteases. Caspases are synthesized as relatively inactive zymogens that become activated by scaffold-mediated transactivation or by cleavage via upstream proteases in an intracellular cascade. Regulation of caspase activation and activity occurs at several different levels: (a) Zymogen gene transcription is regulated; (b) antiapoptotic members of the Bcl-2 family and other cellular polypeptides block proximity-induced activation of certain procaspases; and (c) certain cellular inhibitor of apoptosis proteins (clAPs) can bind to and inhibit active caspases. Once activated, caspases cleave a variety of intracellular polypeptides, including major structural elements of the cytoplasm and nucleus, components of the DNA repair machinery, and a number of protein kinases. Collectively, these scissions disrupt survival pathways and disassemble important architectural components of the cell, contributing to the stereotypic morphological and biochemical changes that characterize apoptotic cell death.

Original languageEnglish (US)
Pages (from-to)383-424
Number of pages42
JournalAnnual Review of Biochemistry
Volume68
DOIs
StatePublished - 1999

Fingerprint

Caspases
Chemical activation
Apoptosis
Peptide Hydrolases
Substrates
Enzyme Precursors
Cell death
Cell Death
Inhibitor of Apoptosis Proteins
Peptides
Cellular Structures
Transcription
Aspartic Acid
Scaffolds
DNA Repair
Protein Kinases
Transcriptional Activation
Machinery
Cysteine
Cytoplasm

Keywords

  • Cell death
  • Proteases
  • Signal transduction
  • Targets
  • Zymogen processing

ASJC Scopus subject areas

  • Biochemistry

Cite this

Mammalian caspases : Structure, activation, substrates, and functions during apoptosis. / Earnshaw, William C.; Martins, Luis M.; Kaufmann, Scott H.

In: Annual Review of Biochemistry, Vol. 68, 1999, p. 383-424.

Research output: Contribution to journalArticle

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