The Drosophila caspase inhibitor DIAP1 is essential for cell survival and is negatively regulated by HID.
Drosophila Reaper (RPR), Head Involution Defective (HID), and GRIM induce caspase-dependent cell death and physically interact with the cell death inhibitor DIAP1. Here we show that HID blocks DIAP1's ability to inhibit caspase activity and provide evidence suggesting that RPR and GRIM can act similarly. Based on these results, we propose that RPR, HID, and GRIM promote apoptosis by disrupting productive IAP-caspase interactions and that DIAP1 is required to block apoptosis-inducing caspase activity. Supporting this hypothesis, we show that elimination of DIAP1 function results in global early embryonic cell death and a large increase in DIAP1-inhibitable caspase activity and that DIAP1 is still required for cell survival when expression of rpr, hid, and grim is eliminated.
Wang
S L
SL
Division of Biology MC 156-29, California Institute of Technology, Pasadena 91125, USA.
Hawkins
C J
CJ
Yoo
S J
SJ
Müller
H A
HA
Hay
B A
BA
D000165:Acridine Orange; D000818:Animals; D017209:Apoptosis / Q000235:genetics / Q000502:physiology*; D061945:Caspase Inhibitors; D029721:Drosophila Proteins; D004331:Drosophila melanogaster / Q000196:embryology / Q000235:genetics / Q000502:physiology*; D004843:Epistasis, Genetic; D005456:Fluorescent Dyes; D005804:Genes, Lethal; D020287:In Situ Nick-End Labeling; D051034:Inhibitor of Apoptosis Proteins; D019476:Insect Proteins / Q000235:genetics / Q000502:physiology*; D009024:Morphogenesis / Q000235:genetics; D009479:Neuropeptides / Q000235:genetics / Q000502:physiology; D010455:Peptides / Q000235:genetics / Q000502:physiology; D011993:Recombinant Fusion Proteins / Q000502:physiology; D012441:Saccharomyces cerevisiae / Q000166:cytology
D061945:Caspase Inhibitors; C111891:DIAP1 protein, Drosophila; D029721:Drosophila Proteins; D005456:Fluorescent Dyes; C108880:HID protein, Drosophila; D051034:Inhibitor of Apoptosis Proteins; D019476:Insect Proteins; D009479:Neuropeptides; D010455:Peptides; D011993:Recombinant Fusion Proteins; C108881:grim protein, Drosophila; C086973:rpr protein, Drosophila; D000165:Acridine Orange