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Bifunctional killing activity encoded by conserved reaper proteins

P Chen1, S-I Ho, Z Shi

  • 1Department of Cell Biology, UT Southwestern Medical Center, Dallas, TX 75390, USA.

Cell Death and Differentiation
|March 6, 2004
PubMed

Insights

Blowfly Reaper protein induces apoptosis in Drosophila by antagonizing IAP proteins. Distinct functional domains within Reaper mediate separate cell death pathways, challenging single-effector models.

Area of Science:

  • * Molecular Biology
  • * Cell Biology
  • * Developmental Biology

Background:

  • * Drosophila Reaper proteins are key activators of apoptosis.
  • * They function by antagonizing Inhibitor of Apoptosis Proteins (IAPs) via a conserved RHG motif.
  • * Understanding the precise mechanisms of Reaper-mediated apoptosis is crucial for cell death research.

Purpose of the Study:

  • * To investigate the functional domains of blowfly Reaper and their role in apoptosis.
  • * To identify distinct killing activities beyond the known RHG motif.
  • * To elucidate the effector pathways involved in Reaper-induced cell death.

Main Methods:

  • * Isolation of Reaper from the blowfly *L. cuprina*.
  • * Expression of conserved Reaper regions using GFP fusions in *Drosophila* cells.
  • * Analysis of apoptosis induction, membrane blebbing, and IAP binding.

Main Results:

  • * Blowfly Reaper triggered extensive apoptosis in *Drosophila* cells.
  • * A 20-amino acid peptide (R3) conferred a novel killing activity, promoting membrane blebbing independently of translational suppression or DIAP1 levels.
  • * A second IAP-binding domain at the C-terminus of Reaper bound DIAP1 but did not induce apoptosis.
  • * R3-induced cell death was only modestly suppressed by Dronc silencing and showed no DIAP1 association.

Conclusions:

  • * Reaper possesses at least two distinct functional domains mediating cell death.
  • * These domains operate through separate effector pathways, challenging single-effector models of Reaper function.
  • * Blowfly Reaper represents a conserved bifunctional death-inducing factor.

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