title: Control of apoptosis by Drosophila DCAF12.
abstract: Regulated Apoptosis (Programmed Cell Death, PCD) maintains tissue homeostasis in adults, and ensures proper growth and morphogenesis of tissues during development of metazoans. Accordingly, defects in cellular processes triggering or executing apoptotic programs have been implicated in a variety of degenerative and neoplastic diseases. Here, we report the identification of DCAF12, an evolutionary conserved member of the WD40-motif repeat family of proteins, as a new regulator of apoptosis in Drosophila. We find that DCAF12 is required for Diap1 cleavage in response to pro-apoptotic signals, and is thus necessary and sufficient for RHG (Reaper, Hid, and Grim)-mediated apoptosis. Loss of DCAF12 perturbs the elimination of supernumerary or proliferation-impaired cells during development, and enhances tumor growth induced by loss of neoplastic tumor suppressors, highlighting the wide requirement for DCAF12 in PCD.
authors.affiliation: Department of Biology, University of Rochester, River Campus Box 270211, Rochester, NY 14627, USA; Department of Biomedical Genetics, University of Rochester School of Medicine and Dentistry, 601 Elmwood Avenue, Rochester, NY 14642, USA.
authors.forename: Dae-Sung
authors.initials: DS
authors.lastname: Hwangbo
authors.affiliation: Department of Biomedical Genetics, University of Rochester School of Medicine and Dentistry, 601 Elmwood Avenue, Rochester, NY 14642, USA.
authors.forename: Benoit
authors.initials: B
authors.lastname: Biteau
authors.affiliation: Department of Biology, University of Rochester, River Campus Box 270211, Rochester, NY 14627, USA.
authors.forename: Sneha
authors.initials: S
authors.lastname: Rath
authors.affiliation: Buck Institute for Research on Aging, 8001 Redwood Boulevard, Novato, CA 94945-1400, USA.
authors.forename: Jihyun
authors.initials: J
authors.lastname: Kim
authors.affiliation: Department of Biology, University of Rochester, River Campus Box 270211, Rochester, NY 14627, USA; Buck Institute for Research on Aging, 8001 Redwood Boulevard, Novato, CA 94945-1400, USA. Electronic address: hjasper@buckinstitute.org.
authors.forename: Heinrich
authors.initials: H
authors.lastname: Jasper
mesh_terms: D000483:Alleles; D000818:Animals; D030801:Animals, Genetically Modified; D017209:Apoptosis; D020169:Caspases / Q000378:metabolism; D049109:Cell Proliferation; D003433:Crosses, Genetic; D029721:Drosophila Proteins / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D004331:Drosophila melanogaster; D005260:Female; D017353:Gene Deletion; D006706:Homeostasis; D006720:Homozygote; D051034:Inhibitor of Apoptosis Proteins / Q000378:metabolism; D008297:Male; D008675:Metamorphosis, Biological; D009024:Morphogenesis; D009154:Mutation; D010641:Phenotype; D012160:Retina / Q000196:embryology
chemical_list: C000610470:DCAF12 protein, Drosophila; C111891:DIAP1 protein, Drosophila; D029721:Drosophila Proteins; D051034:Inhibitor of Apoptosis Proteins; D020169:Caspases
keywords: Apoptosis; DCAF12; DIAP1 cleavage