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Dredd, a novel effector of the apoptosis activators reaper, grim, and hid in Drosophila
P Chen1, A Rodriguez, R Erskine
1Department of Cell Biology and Neuroscience, University of Texas, Southwestern Medical Center, 5323 Harry Hines Boulevard, Dallas, Texas 75235-9039, USA.
Abstract:
Caspases are widely conserved proteases considered to be essential effectors of apoptosis. We identified a novel Drosophila gene, dredd, which shares extensive homology to all members of the caspase gene family. Cells specified for programmed death in development exhibit a striking accumulation of dredd RNA that requires signaling by the death activators REAPER, GRIM, and HID. Furthermore, directed misexpression of each activator was sufficient to drive ectopic accumulation of dredd RNA. Heterozygosity at the dredd locus suppressed apoptosis in transgenic models of reaper- and grim-induced cell killing, demonstrating that levels of dredd product can modulate signaling triggered by these death activators. Finally, expression of REAPER, GRIM, and HID was found to trigger processing of DREDD protein precursor through a mechanism that is insensitive to, and upstream of, known caspase inhibitors. Taken together, these observations establish mechanistic connections between activators of apoptosis and a new downstream death effector in Drosophila.
Insights
Researchers discovered a new gene, dredd, essential for apoptosis (programmed cell death) in Drosophila. Its expression is regulated by key death activators, linking them to this crucial cell-death pathway.
Area of Science:
- Molecular Biology
- Developmental Biology
- Genetics
Background:
- Caspases are critical proteases executing apoptosis.
- Understanding apoptosis regulation is key in developmental biology.
Purpose of the Study:
- To identify novel genes involved in apoptosis regulation in Drosophila.
- To elucidate the mechanistic link between known apoptosis activators and downstream effectors.
Main Methods:
- Gene identification and homology analysis.
- RNA accumulation studies in response to death activators.
- Functional analysis using transgenic Drosophila models.
- Protein processing assays.
Main Results:
- A novel Drosophila gene, dredd, homologous to caspases, was identified.
- dredd RNA accumulation is dependent on death activators REAPER, GRIM, and HID.
- dredd heterozygosity suppresses apoptosis induced by REAPER and GRIM.
- REAPER, GRIM, and HID trigger DREDD protein processing independently of known caspase inhibitors.
Conclusions:
- Dredd is a novel caspase family member and a downstream effector of apoptosis in Drosophila.
- Dredd acts as a crucial link between death activators and the execution of programmed cell death.