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Updated: May 28, 2026
In Vivo Biosensor Tracks Non-apoptotic Caspase Activity in Drosophila
Published on: November 27, 2016
Genome-wide silencing in Drosophila captures conserved apoptotic effectors
Su Kit Chew1, Po Chen, Nichole Link
1Department of Cell Biology, University of Texas Southwestern Medical Center, Dallas, Texas 75390, USA.
Abstract:
Apoptosis is a conserved form of programmed cell death firmly established in the aetiology, pathogenesis and treatment of many human diseases. Central to the core machinery of apoptosis are the caspases and their proximal regulators. Current models for caspase control involve a balance of opposing elements, with variable contributions from positive and negative regulators among different cell types and species. To advance a comprehensive view of components that support caspase-dependent cell death, we conducted a genome-wide silencing screen in the Drosophila model. Our strategy used a library of double-stranded RNAs together with a chemical antagonist of Inhibitor of apoptosis proteins (IAPs) that simulates the action of native regulators in the Reaper and Smac (also known as Diablo) families. Here we present a highly validated set of targets that is necessary for death provoked by several stimuli. Among these, Tango7 is identified as a new effector. Cells depleted for this gene resisted apoptosis at a step before the induction of effector caspase activity, and the directed silencing of Tango7 in Drosophila prevented caspase-dependent programmed cell death. Unlike known apoptosis regulators in this model system, Tango7 activity did not influence stimulus-dependent loss of Drosophila DIAP1 (also known as th and IAP1), but instead regulated levels of the apical caspase Dronc (Nc). Similarly, the human Tango7 counterpart, PCID1 (also known as EIF3M), impinged on caspase 9, revealing a new regulatory axis affecting the apoptosome.
Insights
Researchers identified Tango7 as a novel effector in programmed cell death. Silencing Tango7 in Drosophila prevented apoptosis by regulating the apical caspase Dronc, revealing a new axis in cell death regulation.
Area of Science:
- Cell Biology
- Genetics
- Biochemistry
Background:
- Apoptosis, or programmed cell death, is crucial in human diseases and involves caspases and their regulators.
- Existing models of caspase control show a balance of positive and negative regulators, varying by cell type and species.
Purpose of the Study:
- To identify novel components regulating caspase-dependent cell death using a genome-wide screen.
- To elucidate the role of newly identified genes in apoptosis pathways.
Main Methods:
- Conducted a genome-wide RNA interference (RNAi) screen in Drosophila.
- Utilized a double-stranded RNA library and a chemical antagonist of Inhibitor of Apoptosis Proteins (IAPs).
- Validated identified targets for their necessity in stimulus-induced cell death.
Main Results:
- Identified a validated set of genes essential for apoptosis.
- Discovered Tango7 as a novel effector; its depletion prevented apoptosis before effector caspase activation.
- Tango7 regulated the apical caspase Dronc in Drosophila, distinct from DIAP1 regulation.
- The human homolog of Tango7, PCID1, influenced caspase 9, indicating a conserved regulatory role.
Conclusions:
- Tango7 is a novel effector in the apoptosis pathway, regulating apical caspase activity.
- A new regulatory axis involving Tango7/PCID1 and apical caspases (Dronc/caspase 9) has been uncovered.
- This discovery provides new insights into the mechanisms of programmed cell death and potential therapeutic targets.
