title: The SCF ubiquitin ligase protein slimb regulates centrosome duplication in Drosophila.
abstract: The duplication of the centrosome is a key event in the cell-division cycle. Although defects in centrosome duplication are thought to contribute to genomic instability [1-3] and are a hallmark of certain transformed cells and human cancer [4-6], the mechanism responsible for centrosome duplication is not understood. Recent experiments have established that centrosome duplication requires the activity of cyclin-dependent kinase 2 (Cdk2) and cyclins E and A [7-9]. The stability of cyclin E is regulated by the ubiquitin ligase SCF, which is a protein complex composed of Skp1, Cdc53 (Cullin) and F-box proteins [10-12]. The Skp1 and Cullin components have been detected on mammalian centrosomes, and shown to be essential for centrosome duplication and separation in Xenopus [13]. Here, we report that Slimb, an F-box protein that targets proteins to the SCFcomplex [14,15], plays a role in limiting centrosome replication. We found that, in the fruit fly Drosophila, the hypomorphic mutation slimb(crd) causes the appearance of additional centrosomes and mitotic defects in mutant larval neuroblasts.
authors.affiliation: Department of Biology, Virginia Tech University, Blacksburg, Virginia, 24061, USA. ewojcik@vt.edu
authors.forename: E J
authors.initials: EJ
authors.lastname: Wojcik
authors.forename: D M
authors.initials: DM
authors.lastname: Glover
authors.forename: T S
authors.initials: TS
authors.lastname: Hays
mesh_terms: D000818:Animals; D001921:Brain / Q000166:cytology; D018797:Cell Cycle Proteins / Q000235:genetics / Q000378:metabolism*; D018385:Centrosome / Q000378:metabolism*; D004330:Drosophila / Q000235:genetics / Q000378:metabolism*; D029721:Drosophila Proteins; D005455:Fluorescent Antibody Technique; D019476:Insect Proteins / Q000235:genetics / Q000378:metabolism*; D007814:Larva / Q000166:cytology; D018613:Microscopy, Confocal; D008938:Mitosis / Q000502:physiology; D009154:Mutation; D010453:Peptide Synthases / Q000235:genetics; D011123:Polyploidy; D044843:SKP Cullin F-Box Protein Ligases; D044767:Ubiquitin-Protein Ligases
chemical_list: D018797:Cell Cycle Proteins; D029721:Drosophila Proteins; D019476:Insect Proteins; C110233:slmb protein, Drosophila; D044843:SKP Cullin F-Box Protein Ligases; D044767:Ubiquitin-Protein Ligases; D010453:Peptide Synthases