The Drosophila caspase DRONC is regulated by DIAP1

P Meier1, J Silke, S J Leevers

  • 1Biochemistry of the Cell Nucleus Laboratory, Imperial Cancer Research Fund, 44 Lincoln's Inn Fields, London WC2A 3PX.

The EMBO Journal
|February 17, 2000
PubMed

Insights

Researchers identified the Drosophila caspase DRONC, a p35-resistant caspase. Its pro-domain interacts with DIAP1, inhibiting cell death and implicating DRONC in the reaper pathway.

Area of Science:

  • Molecular Biology
  • Developmental Biology
  • Cell Death Research

Background:

  • Caspases are key regulators of apoptosis.
  • Drosophila melanogaster serves as a model organism for studying apoptosis.
  • The inhibitor of apoptosis protein 1 (DIAP1) is a known regulator of cell death in Drosophila.

Purpose of the Study:

  • To isolate and characterize the Drosophila caspase DRONC.
  • To investigate the interaction of DRONC with other apoptosis regulators like DIAP1.
  • To determine the role of DRONC in developmental cell death pathways.

Main Methods:

  • Yeast two-hybrid screening to identify interacting proteins.
  • Ectopic gene expression in various model systems (yeast, mammalian cells, Drosophila eye).
  • In vitro cleavage assays and in vivo rescue experiments.

Main Results:

  • DRONC was isolated and shown to induce cell death across different species.
  • DRONC is resistant to the caspase inhibitor p35.
  • DIAP1 interacts with the DRONC pro-domain, suppressing DRONC-induced cell death, and DRONC functions in the reaper/head involution defective pathway.

Conclusions:

  • DRONC is a novel, p35-resistant caspase involved in apoptosis.
  • DIAP1 antagonizes DRONC activity through interaction with its pro-domain.
  • DRONC is a crucial component of the reaper-mediated cell death pathway in Drosophila development.

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