Drosophila skpA, a component of SCF ubiquitin ligases, regulates centrosome duplication independently of cyclin E accumulation.
Centrosome duplication must be coupled to the main cell cycle to ensure that each cell has precisely two centrosomes at the onset of mitosis. Supernumerary centrosomes are commonly observed in cancer cells, and may contribute to tumorigenesis. Drosophila skpA, a component of SCF ubiquitin ligases, regulates the link between the cell and centrosome cycles. Lethal skpA null mutants exhibit dramatic centrosome overduplication and additional defects in chromatin condensation, cell cycle progression and endoreduplication. Surprisingly, many mutant cells are able to organize pseudo-bipolar spindles and execute a normal anaphase in the presence of extra functional centrosomes. SkpA mutant cells accumulate higher levels of cyclin E than wildtype cells during S and G2, suggesting that elevated cdk2/cyclin E activity may account for the supernumerary centrosomes in skpA- cells. However, centrosome overduplication still occurs in skpA-; cycE- mutant animals, demonstrating that high cyclin E levels are not necessary for centrosome overduplication. These data suggest that additional SCF targets regulate the centrosome duplication pathway.
Murphy
Terence D
TD
Department of Embryology, Carnegie Institution of Washington, Baltimore, MD 21210, USA. tmurphy@ciwemb.edu
D000818:Animals; D002453:Cell Cycle / Q000502:physiology; D002467:Cell Nucleus / Q000378:metabolism; D018385:Centrosome / Q000378:metabolism*; D019927:Cyclin E / Q000235:genetics / Q000378:metabolism*; D003593:Cytoplasm / Q000378:metabolism; D004330:Drosophila; D029721:Drosophila Proteins / Q000235:genetics / Q000378:metabolism*; D005804:Genes, Lethal; D022101:Microtubule-Organizing Center / Q000378:metabolism; D009154:Mutation; D044843:SKP Cullin F-Box Protein Ligases / Q000235:genetics / Q000378:metabolism*
D019927:Cyclin E; D029721:Drosophila Proteins; C434749:SkpA protein, Drosophila; D044843:SKP Cullin F-Box Protein Ligases