Caspase activation - Stepping on the gas or releasing the brakes? Lessons from humans and flies

Guy S. Salvesen, John M. Abrams

Research output: Contribution to journalReview articlepeer-review

199 Scopus citations

Abstract

The central components of the execution phase of apoptosis in worms, flies, and humans are members of the caspase protease family. Work in Drosophila and mammalian systems has revealed a web of interactions that govern the activity of these proteases, and two fundamental control points have been identified. These are zymogen activation - the process that converts a latent caspase into its active form, and inhibition of the resulting active protease. In humans, the driving force for caspase activity is activation of the zymogens, but in Drosophila, a major thrust is derepression of caspase inhibitors. In this review, we consider evidence for these two distinct events in terms of the regulation of caspase activity. This sets the scene for therapy to reinstate the normal death mechanisms that have been overcome in a cancer cell's quest for immortality.

Original languageEnglish (US)
Pages (from-to)2774-2784
Number of pages11
JournalOncogene
Volume23
Issue number16 REV. ISS. 2
DOIs
StatePublished - Apr 12 2004

Keywords

  • Apoptosis
  • Caspase
  • Drosophila
  • IAP
  • Zymogen activation

ASJC Scopus subject areas

  • Molecular Biology
  • Genetics
  • Cancer Research

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