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Lighting Up the Pathways to Caspase Activation Using Bimolecular Fluorescence Complementation
08:47

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Published on: March 5, 2018

Caspase-2 can function upstream of bid cleavage in the TRAIL apoptosis pathway

Klaus W Wagner1, Ingo H Engels, Quinn L Deveraux

  • 1Department of Cancer Biology, Genomics Institute of the Novartis Research Foundation, 10675 John Jay Hopkins Drive, San Diego, CA 92121, USA.

The Journal of Biological Chemistry
|June 3, 2004
PubMed

Insights

Caspase-2 is essential for optimal TRAIL-mediated apoptosis in type II cells by enabling the cleavage of Bid. This finding highlights a new role for caspase-2 in regulating programmed cell death pathways.

Area of Science:

  • Cell Biology
  • Molecular Biology
  • Biochemistry

Background:

  • TRAIL/Apo2L binding to DR4/DR5 receptors triggers apoptosis.
  • In type II cells, caspase-8 cleaves Bid, initiating apoptosis.
  • Mitochondrial outer membrane permeabilization releases pro-apoptotic factors.

Purpose of the Study:

  • Investigate the role of caspase-2 in TRAIL-mediated apoptosis.
  • Determine if caspase-2 is required for Bid cleavage in type II cells.

Main Methods:

  • RNA interference to down-regulate caspase-2 expression.
  • Analysis of the TRAIL proteolytic cascade.
  • Gene silencing of specific pathway components.

Main Results:

  • Caspase-2 down-regulation significantly inhibited TRAIL-induced apoptosis.
  • Caspase-2 is necessary for efficient Bid cleavage in type II cells.
  • Caspase-2 processing downstream of Bax is not required for Bid cleavage.

Conclusions:

  • Caspase-2 plays a critical role in TRAIL-mediated apoptosis.
  • Caspase-2 acts upstream of or parallel to Bid cleavage in this pathway.
  • These findings reveal a novel function for caspase-2 in programmed cell death.

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