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08:47

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Published on: March 5, 2018

Caspase-10 triggers Bid cleavage and caspase cascade activation in FasL-induced apoptosis

Delphine Milhas1, Olivier Cuvillier, Nicole Therville

  • 1INSERM U466, Institut Louis Bugnard, Toulouse, France.

The Journal of Biological Chemistry
|March 18, 2005
PubMed

Insights

Caspase-10 initiates apoptosis via Fas signaling, activating other caspases and causing DNA fragmentation. This pathway is crucial for cell death, though a caspase-independent route also exists.

Area of Science:

  • Cell Biology
  • Molecular Biology
  • Immunology

Background:

  • Controversy exists regarding caspase-10's role in FasL-mediated apoptosis, unlike the established role of caspase-8.
  • Understanding initiator caspases in apoptosis is vital for cell death research.

Purpose of the Study:

  • To investigate the role of caspase-10 in FasL-induced apoptosis.
  • To elucidate the signaling pathway involving caspase-10 in Jurkat cells.

Main Methods:

  • Utilized caspase-8-deficient Jurkat (I9-2) cells treated with FasL.
  • Assessed caspase activation, Bid cleavage, cytochrome c release, and DNA fragmentation.
  • Employed specific caspase inhibitors (benzyloxycarbonyl-VAD-fluoromethyl ketone and benzyloxycarbonyl-AEVD-fluoromethyl ketone).

Main Results:

  • FasL treatment activated caspase-10, -3, and -7, leading to Bid cleavage and cytochrome c release in caspase-8-deficient cells.
  • Apoptosis, evidenced by DNA fragmentation, was inhibited by caspase inhibitors, confirming caspase involvement.
  • Cell sensitivity to FasL correlated with caspase-10 expression levels.
  • Caspase-10, like caspase-8, could cleave Bid in vitro.

Conclusions:

  • Caspase-10 acts as an initiator caspase in Fas signaling, triggering a caspase cascade and apoptosis.
  • A caspase-independent pathway contributes to FasL-induced cell death.
  • Caspase-10's role in apoptosis is dependent on its expression level.

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