The COP9 signalosome promotes degradation of Cyclin E during early Drosophila oogenesis.
The COP9 signalosome (CSN) is an eight-subunit complex that regulates multiple signaling and cell cycle pathways. Here we link the CSN to the degradation of Cyclin E, which promotes the G1-S transition in the cell cycle and then is rapidly degraded by the ubiquitin-proteasome pathway. Using CSN4 and CSN5/Jab1 mutants, we show that the CSN acts during Drosophila oogenesis to remove Nedd8 from Cullin1, a subunit of the SCF ubiquitin ligase. Overexpression of Cyclin E causes similar defects as mutations in CSN or SCF(Ago) subunits: extra divisions or, in contrast, cell cycle arrest and polyploidy. Because the phenotypes are so similar and because CSN and Cyclin E mutations reciprocally suppress each other, Cyclin E appears to be the major target of the CSN during early oogenesis. Genetic interactions among CSN, SCF, and proteasome subunits further confirm CSN involvement in ubiquitin-mediated Cyclin E degradation.
Department of Molecular and Cell Biology, University of California, Berkeley, 401 Barker Hall, Berkeley, CA 94720, USA.
Sergey
S
Doronkin
Inna
I
Djagaeva
Steven K
SK
Beckendorf
D000818:Animals; D000075686:COP9 Signalosome Complex; D018797:Cell Cycle Proteins / Q000235:genetics / Q000378:metabolism; D019927:Cyclin E / Q000378:metabolism*; D004330:Drosophila / Q000166:cytology* / Q000235:genetics / Q000254:growth & development / Q000378:metabolism; D005260:Female; D008540:Meiosis; D008938:Mitosis; D046912:Multiprotein Complexes; D009154:Mutation; D009866:Oogenesis; D010447:Peptide Hydrolases; D010641:Phenotype; D011506:Proteins / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction
D018797:Cell Cycle Proteins; D019927:Cyclin E; D046912:Multiprotein Complexes; D011506:Proteins; D010447:Peptide Hydrolases; D000075686:COP9 Signalosome Complex