title: A novel F-box protein is required for caspase activation during cellular remodeling in Drosophila.
abstract: Terminal differentiation of male germ cells in Drosophila and mammals requires extensive cytoarchitectural remodeling, the elimination of many organelles, and a large reduction in cell volume. The associated process, termed spermatid individualization, is facilitated by the apoptotic machinery, including caspases, but does not result in cell death. From a screen for genes defective in caspase activation in this system, we isolated a novel F-box protein, which we termed Nutcracker, that is strictly required for caspase activation and sperm differentiation. Nutcracker interacts through its F-box domain with members of a Cullin-1-based ubiquitin ligase complex (SCF): Cullin-1 and SkpA. This ubiquitin ligase does not regulate the stability of the caspase inhibitors DIAP1 and DIAP2, but physically binds Bruce, a BIR-containing giant protein involved in apoptosis regulation. Furthermore, nutcracker mutants disrupt proteasome activity without affecting their distribution. These findings define a new SCF complex required for caspase activation during sperm differentiation and highlight the role of regulated proteolysis during this process.
authors.affiliation: Howard Hughes Medical Institute, The Rockefeller University, New York, NY 10021, USA.
authors.forename: Maya
authors.initials: M
authors.lastname: Bader
authors.forename: Eli
authors.initials: E
authors.lastname: Arama
authors.forename: Hermann
authors.initials: H
authors.lastname: Steller
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D030801:Animals, Genetically Modified; D020169:Caspases / Q000378:metabolism*; D002454:Cell Differentiation / Q000235:genetics* / Q000502:physiology; D004330:Drosophila / Q000235:genetics* / Q000378:metabolism / Q000502:physiology; D029721:Drosophila Proteins / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D004789:Enzyme Activation / Q000235:genetics; D044783:F-Box Proteins / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D007248:Infertility, Male / Q000235:genetics / Q000378:metabolism; D008297:Male; D008954:Models, Biological; D008969:Molecular Sequence Data; D017386:Sequence Homology, Amino Acid; D013094:Spermatozoa / Q000378:metabolism / Q000502:physiology* / Q000648:ultrastructure; D013737:Testis / Q000378:metabolism / Q000502:physiology
chemical_list: D029721:Drosophila Proteins; D044783:F-Box Proteins; C549614:ntc protein, Drosophila; D020169:Caspases
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