A Conserved F Box Regulatory Complex Controls Proteasome Activity in Drosophila

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...

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Bibliographic Details
Published in:Cell 2011-04, Vol.145 (3), p.371-382
Main Authors: Bader, Maya, Benjamin, Sigi, Wapinski, Orly L., Smith, David M., Goldberg, Alfred L., Steller, Hermann
Format: Article
Language:English
Subjects:
Amino Acid Sequence
Animals
Carrier Proteins - genetics
Carrier Proteins - metabolism
caspases
Caspases - metabolism
cell cycle
Cell Line
Drosophila
Drosophila melanogaster - cytology
Drosophila melanogaster - physiology
Drosophila Proteins - analysis
Drosophila Proteins - genetics
Drosophila Proteins - metabolism
F-Box Proteins - metabolism
Humans
Male
mammals
Mice
Molecular Sequence Data
proteasome endopeptidase complex
Proteasome Endopeptidase Complex - metabolism
protein degradation
proteins
Proteome - analysis
Sequence Alignment
sperm
Spermatogenesis
spermatozoa
Testis - metabolism
ubiquitin-protein ligase
ubiquitination
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Summary: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. [Display omitted] ► A conserved mode of proteasome regulation ► An SCF ubiquitin-ligase regulates a proteasome activator, PI31 ► Drosophila PI31 is an essential protein, required for normal proteasome activity ► Caspases and proteasomes are coordinately regulated during cell remodeling
ISSN:0092-8674
1097-4172
DOI:10.1016/j.cell.2011.03.021