A novel F-box protein is required for caspase activation during cellular remodeling in Drosophila.
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.
Bader
Maya
M
Howard Hughes Medical Institute, The Rockefeller University, New York, NY 10021, USA.
Arama
Eli
E
Steller
Hermann
H
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
D029721:Drosophila Proteins; D044783:F-Box Proteins; C549614:ntc protein, Drosophila; D020169:Caspases
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