title: Regulation of Drosophila IAP1 degradation and apoptosis by reaper and ubcD1.
abstract: 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.
authors.affiliation: Howard Hughes Medical Institute, Strang Laboratory of Cancer Research, The Rockefeller University Box 252, 1230 York Ave. New York, NY 10021, USA.
authors.forename: Hyung Don
authors.initials: HD
authors.lastname: Ryoo
authors.forename: Andreas
authors.initials: A
authors.lastname: Bergmann
authors.forename: Hedva
authors.initials: H
authors.lastname: Gonen
authors.forename: Aaron
authors.initials: A
authors.lastname: Ciechanover
authors.forename: Hermann
authors.initials: H
authors.lastname: Steller
mesh_terms: 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
chemical_list: 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