title: A conserved F box regulatory complex controls proteasome activity in Drosophila.
abstract: The ubiquitin-proteasome system catalyzes the degradation of intracellular proteins. Although ubiquitination of proteins determines their stabilities, there is growing evidence that proteasome function is also regulated. We report the functional characterization of a conserved proteasomal regulatory complex. We identified DmPI31 as a binding partner of the F box protein Nutcracker, a component of an SCF ubiquitin ligase (E3) required for caspase activation during sperm differentiation in Drosophila. DmPI31 binds Nutcracker via a conserved mechanism that is also used by mammalian FBXO7 and PI31. Nutcracker promotes DmPI31 stability, which is necessary for caspase activation, proteasome function, and sperm differentiation. DmPI31 can activate 26S proteasomes in vitro, and increasing DmPI31 levels suppresses defects caused by diminished proteasome activity in vivo. Furthermore, loss of DmPI31 function causes lethality, cell-cycle abnormalities, and defects in protein degradation, demonstrating that DmPI31 is physiologically required for normal proteasome activity.
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: Sigi
authors.initials: S
authors.lastname: Benjamin
authors.forename: Orly L
authors.initials: OL
authors.lastname: Wapinski
authors.forename: David M
authors.initials: DM
authors.lastname: Smith
authors.forename: Alfred L
authors.initials: AL
authors.lastname: Goldberg
authors.forename: Hermann
authors.initials: H
authors.lastname: Steller
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism*; D020169:Caspases / Q000378:metabolism; D002460:Cell Line; D029721:Drosophila Proteins / Q000032:analysis / Q000235:genetics / Q000378:metabolism*; D004331:Drosophila melanogaster / Q000166:cytology* / Q000502:physiology*; D044783:F-Box Proteins / Q000378:metabolism*; D006801:Humans; D008297:Male; D051379:Mice; D008969:Molecular Sequence Data; D046988:Proteasome Endopeptidase Complex / Q000378:metabolism*; D020543:Proteome / Q000032:analysis; D016415:Sequence Alignment; D013091:Spermatogenesis; D013737:Testis / Q000378:metabolism
chemical_list: D002352:Carrier Proteins; D029721:Drosophila Proteins; D044783:F-Box Proteins; C558902:PI31 protein, Drosophila; D020543:Proteome; C549614:ntc protein, Drosophila; D020169:Caspases; D046988:Proteasome Endopeptidase Complex