The role of ARK in stress-induced apoptosis in Drosophila cells.
The molecular mechanisms of apoptosis are highly conserved throughout evolution. The homologs of genes essential for apoptosis in Caenorhabditis elegans and Drosophila melanogaster have been shown to be important for apoptosis in mammalian systems. Although a homologue for CED-4/apoptotic protease-activating factor (Apaf)-1 has been described in Drosophila, its exact function and the role of the mitochondrial pathway in its activation remain unclear. Here, we used the technique of RNA interference to dissect apoptotic signaling pathways in Drosophila cells. Inhibition of the Drosophila CED-4/Apaf-1-related killer (ARK) homologue resulted in pronounced inhibition of stress-induced apoptosis, whereas loss of ARK did not protect the cells from Reaper- or Grim-induced cell death. Reduction of DIAP1 induced rapid apoptosis in these cells, whereas the inhibition of DIAP2 expression did not but resulted in increased sensitivity to stress-induced apoptosis; apoptosis in both cases was prevented by inhibition of ARK expression. Cells in which cytochrome c expression was decreased underwent apoptosis induced by stress stimuli, Reaper or Grim. These results demonstrate the central role of ARK in stress-induced apoptosis, which appears to act independently of cytochrome c. Apoptosis induced by Reaper or Grim can proceed via a distinct pathway, independent of ARK.
Zimmermann
Katja C
KC
Division of Cellular Immunology, La Jolla Institute for Allergy and Immunology, San Diego, California 92121, USA.
Ricci
Jean-Ehrland
JE
Droin
Nathalie M
NM
Green
Douglas R
DR
D000818:Animals; D017209:Apoptosis / Q000235:genetics*; D053477:Apoptotic Protease-Activating Factor 1; D029742:Caenorhabditis elegans Proteins; D002135:Calcium-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D061945:Caspase Inhibitors; D020169:Caspases / Q000235:genetics / Q000378:metabolism; D003574:Cytochrome c Group / Q000187:drug effects / Q000235:genetics / Q000378:metabolism; D015536:Down-Regulation / Q000187:drug effects / Q000502:physiology; D029721:Drosophila Proteins; D004331:Drosophila melanogaster / Q000166:cytology / Q000235:genetics / Q000378:metabolism*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D015801:Helminth Proteins / Q000235:genetics / Q000378:metabolism*; D051034:Inhibitor of Apoptosis Proteins; D019476:Insect Proteins / Q000235:genetics / Q000378:metabolism; D008564:Membrane Potentials / Q000187:drug effects / Q000502:physiology; D008928:Mitochondria / Q000187:drug effects / Q000378:metabolism; D009479:Neuropeptides / Q000235:genetics / Q000378:metabolism; D010455:Peptides / Q000235:genetics / Q000378:metabolism; D011506:Proteins / Q000235:genetics / Q000378:metabolism*; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000037:antagonists & inhibitors / Q000378:metabolism; D012330:RNA, Double-Stranded / Q000235:genetics / Q000494:pharmacology; D013312:Stress, Physiological / Q000235:genetics / Q000378:metabolism* / Q000503:physiopathology; D014466:Ultraviolet Rays
D053477:Apoptotic Protease-Activating Factor 1; D029742:Caenorhabditis elegans Proteins; D002135:Calcium-Binding Proteins; D061945:Caspase Inhibitors; C089224:Ced-4 protein, C elegans; D003574:Cytochrome c Group; C111891:DIAP1 protein, Drosophila; C111892:DIAP2 protein, Drosophila; D029721:Drosophila Proteins; D004791:Enzyme Inhibitors; D015801:Helminth Proteins; D051034:Inhibitor of Apoptosis Proteins; D019476:Insect Proteins; D009479:Neuropeptides; D010455:Peptides; D011506:Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; D012330:RNA, Double-Stranded; C400550:dark protein, Drosophila; C108881:grim protein, Drosophila; C086973:rpr protein, Drosophila; D020169:Caspases