Regulation of Drosophila IAP1 degradation and apoptosis by reaper and ubcD1.
Cell death in higher organisms is negatively regulated by Inhibitor of Apoptosis Proteins (IAPs), which contain a ubiquitin ligase motif, but how ubiquitin-mediated protein degradation is regulated during apoptosis is poorly understood. Here, we report that Drosophila melanogaster IAP1 (DIAP1) auto-ubiquitination and degradation is actively regulated by Reaper (Rpr) and UBCD1. We show that Rpr, but not Hid (head involution defective), promotes significant DIAP1 degradation. Rpr-mediated DIAP1 degradation requires an intact DIAP1 RING domain. Among the mutations affecting ubiquitination, we found ubcD1, which suppresses rpr-induced apoptosis. UBCD1 and Rpr specifically bind to DIAP1 and stimulate DIAP1 auto-ubiquitination in vitro. Our results identify a novel function of Rpr in stimulating DIAP1 auto-ubiquitination through UBCD1, thereby promoting its degradation.
Ryoo
Hyung Don
HD
Howard Hughes Medical Institute, Strang Laboratory of Cancer Research, The Rockefeller University Box 252, 1230 York Ave. New York, NY 10021, USA.
Bergmann
Andreas
A
Gonen
Hedva
H
Ciechanover
Aaron
A
Steller
Hermann
H
D000367:Age Factors; D000818:Animals; D017209:Apoptosis / Q000502:physiology*; D020169:Caspases / Q000378:metabolism; D002452:Cell Count; D029721:Drosophila Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D004331:Drosophila melanogaster; D018507:Gene Expression Regulation, Developmental; D066298:In Vitro Techniques; D051034:Inhibitor of Apoptosis Proteins; D008025:Ligases / Q000235:genetics / Q000378:metabolism*; D016296:Mutagenesis / Q000502:physiology; D009475:Neurons, Afferent / Q000166:cytology; D009479:Neuropeptides / Q000235:genetics / Q000378:metabolism; D010455:Peptides / Q000235:genetics / Q000378:metabolism*; D011485:Protein Binding / Q000502:physiology; D017434:Protein Structure, Tertiary; D012323:RNA Processing, Post-Transcriptional / Q000502:physiology; D025801:Ubiquitin / Q000378:metabolism; D044763:Ubiquitin-Conjugating Enzymes
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; D044763:Ubiquitin-Conjugating Enzymes; C471611:eff protein, Drosophila; D020169:Caspases; D008025:Ligases