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.
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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.
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| uniprot:name |
Dev. Cell
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| uniprot:author |
Beckendorf S.K.,
Djagaeva I.,
Doronkin S.
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| uniprot:date |
2003
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| uniprot:pages |
699-710
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| uniprot:title |
The COP9 signalosome promotes degradation of Cyclin E during early Drosophila oogenesis.
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| uniprot:volume |
4
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| dc-term:identifier |
doi:10.1016/S1534-5807(03)00121-7
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