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First published online October 22, 2003
doi: 10.1242/10.1242/jcs.00783

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DIAP1 suppresses ROS-induced apoptosis caused by impairment of the selD/sps1 homolog in Drosophila

Departament de Genètica, Facultat de Biologia, Universitat de Barcelona, Diagonal 645, 08028 Barcelona, Spain

^* Author for correspondence (e-mail: fserras{at}ub.edu)

Accepted 21 July 2003

The cellular antioxidant defense systems neutralize the cytotoxic by-products referred to as reactive oxygen species (ROS). Among them, selenoproteins have important antioxidant and detoxification functions. The interference in selenoprotein biosynthesis results in accumulation of ROS and consequently in a toxic intracellular environment. The resulting ROS imbalance can trigger apoptosis to eliminate the deleterious cells. In Drosophila, a null mutation in the selD gene (homologous to the human selenophosphate synthetase type 1) causes an impairment of selenoprotein biosynthesis, a ROS burst and lethality. We propose this mutation (known as selD^ptuf) as a tool to understand the link between ROS accumulation and cell death. To this aim we have analyzed the mechanism by which selD^ptuf mutant cells become apoptotic in Drosophila imaginal discs. The apoptotic effect of selD^ptuf does not require the activity of the Ras/MAPK-dependent proapoptotic gene hid, but results in stabilization of the tumor suppressor protein Dmp53 and transcription of the Drosophila pro-apoptotic gene reaper (rpr). We also provide genetic evidence that the initiator caspase DRONC is activated and that the effector caspase DRICE is processed to commit selD^ptuf mutant cells to death. Moreover, the ectopic expression of the inhibitor of apoptosis DIAP1 rescues the cellular viability of selD^ptuf mutant cells. These observations indicate that selD^ptuf ROS-induced apoptosis in Drosophila is mainly driven by the caspase-dependent Dmp53/Rpr pathway.

Key words: Reaper, p53, DIAP1, SelD, Selenoprotein, ROS

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