The COP9 signalosome promotes degradation of Cyclin E during early Drosophila oogenesis

Dev Cell. 2003 May;4(5):699-710. doi: 10.1016/s1534-5807(03)00121-7.


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.

MeSH terms

  • Animals
  • COP9 Signalosome Complex
  • Cell Cycle Proteins / genetics
  • Cell Cycle Proteins / metabolism
  • Cyclin E / metabolism*
  • Drosophila / cytology*
  • Drosophila / genetics
  • Drosophila / growth & development
  • Drosophila / metabolism
  • Female
  • Meiosis
  • Mitosis
  • Multiprotein Complexes
  • Mutation
  • Oogenesis*
  • Peptide Hydrolases
  • Phenotype
  • Proteins / genetics
  • Proteins / metabolism*
  • Signal Transduction


  • Cell Cycle Proteins
  • Cyclin E
  • Multiprotein Complexes
  • Proteins
  • Peptide Hydrolases
  • COP9 Signalosome Complex