The DIAP1 RING finger mediates ubiquitination of Dronc and is indispensable for regulating apoptosis.
Members of the Inhibitor of Apoptosis Protein (IAP) family block activation of the intrinsic cell death machinery by binding to and neutralizing the activity of pro-apoptotic caspases. In Drosophila melanogaster, the pro-apoptotic proteins Reaper (Rpr), Grim and Hid (head involution defective) all induce cell death by antagonizing the anti-apoptotic activity of Drosophila IAP1 (DIAP1), thereby liberating caspases. Here, we show that in vivo, the RING finger of DIAP1 is essential for the regulation of apoptosis induced by Rpr, Hid and Dronc. Furthermore, we show that the RING finger of DIAP1 promotes the ubiquitination of both itself and of Dronc. Disruption of the DIAP1 RING finger does not inhibit its binding to Rpr, Hid or Dronc, but completely abrogates ubiquitination of Dronc. Our data suggest that IAPs suppress apoptosis by binding to and targeting caspases for ubiquitination.
Wilson
Rebecca
R
The Breakthrough Toby Robins Breast Cancer Research Centre, Institute of Cancer Research, Chester Beatty Laboratories, Fulham Road, London SW3 6JB, UK.
Goyal
Lakshmi
L
Ditzel
Mark
M
Zachariou
Anna
A
Baker
David A
DA
Agapite
Julie
J
Steller
Hermann
H
Meier
Pascal
P
D000818:Animals; D017209:Apoptosis / Q000502:physiology*; D020169:Caspases / Q000378:metabolism*; D002478:Cells, Cultured; D004330:Drosophila; D029721:Drosophila Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D051034:Inhibitor of Apoptosis Proteins; D008025:Ligases / Q000378:metabolism; D016296:Mutagenesis / Q000502:physiology; D009479:Neuropeptides / Q000378:metabolism; D010455:Peptides / Q000378:metabolism; D017956:Photoreceptor Cells, Invertebrate / Q000166:cytology / Q000201:enzymology; D011485:Protein Binding / Q000502:physiology; D017434:Protein Structure, Tertiary; D012160:Retina / Q000166:cytology / Q000201:enzymology; D025801:Ubiquitin / Q000378:metabolism*; D044767:Ubiquitin-Protein Ligases
C111891:DIAP1 protein, Drosophila; D029721:Drosophila Proteins; C108880:HID protein, Drosophila; D051034:Inhibitor of Apoptosis Proteins; D009479:Neuropeptides; D010455:Peptides; D025801:Ubiquitin; C086973:rpr protein, Drosophila; D044767:Ubiquitin-Protein Ligases; D020169:Caspases; C118731:dronc protein, Drosophila; D008025:Ligases