Regulation of apoptosis in Drosophila.
Insects have made major contributions to understanding the regulation of cell death, dating back to the pioneering work of Lockshin and Williams on death of muscle cells during postembryonic development of Manduca. A physically smaller cousin of moths, the fruit fly Drosophila melanogaster, offers unique advantages for studying the regulation of cell death in response to different apoptotic stimuli in situ. Different signaling pathways converge in Drosophila to activate a common death program through transcriptional activation of reaper, hid and grim. Reaper-family proteins induce apoptosis by binding to and antagonizing inhibitor of apoptosis proteins (IAPs), which in turn inhibit caspases. This switch from life to death relies extensively on targeted degradation of cell death proteins by the ubiquitin-proteasome pathway. Drosophila IAP-1 (Diap1) functions as an E3-ubiquitin ligase to protect cells from unwanted death by promoting the degradation of the initiator caspase Dronc. However, in response to apoptotic signals, Reaper-family proteins are produced, which promote the auto-ubiquitination and degradation of Diap1, thereby removing the 'brakes on death' in cells that are doomed to die. More recently, several other ubiquitin pathway proteins were found to play important roles for caspase regulation, indicating that the control of cell survival and death relies extensively on targeted degradation by the ubiquitin-proteasome pathway.
Steller
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Howard Hughes Medical Institute, Rockefeller University, 1230 York Avenue, New York, NY 10065, USA. steller@rockefeller.edu
D000818:Animals; D017209:Apoptosis; D051017:Apoptosis Regulatory Proteins / Q000378:metabolism*; D020169:Caspases / Q000378:metabolism; D029721:Drosophila Proteins / Q000378:metabolism*; D004331:Drosophila melanogaster / Q000201:enzymology / Q000378:metabolism*; D051034:Inhibitor of Apoptosis Proteins / Q000378:metabolism; D046988:Proteasome Endopeptidase Complex / Q000378:metabolism; D012038:Regeneration; D015398:Signal Transduction; D025801:Ubiquitin / Q000378:metabolism
D051017:Apoptosis Regulatory Proteins; D029721:Drosophila Proteins; D051034:Inhibitor of Apoptosis Proteins; D025801:Ubiquitin; C086973:rpr protein, Drosophila; D020169:Caspases; D046988:Proteasome Endopeptidase Complex