title: The C. elegans F-box proteins LIN-23 and SEL-10 antagonize centrosome duplication by regulating ZYG-1 levels.
abstract: The correct segregation of DNA during cell division requires formation of a bipolar spindle, organized at each pole by a centrosome. The regulation of centrosome duplication such that each mitotic cell has exactly two centrosomes is therefore of central importance to cell division. Deregulation of centrosome duplication causes the appearance of supernumerary centrosomes, which are a hallmark of many cancer cells and can contribute to tumorigenesis. Overexpression of the kinase Plk4, which is required for centrosome duplication, causes the formation of extra centrosomes, and aberrant Plk4 expression levels are associated with cancer. Data from Drosophila and human cells show that Plk4 levels are regulated by the SCF ubiquitin ligase and proteasomal degradation. Recognition of Plk4 by the SCF complex is mediated by the F-box protein Slimb/βTrCP. We show that levels of the C. elegans Plk4 homolog ZYG-1 are elevated by impairing proteasome or SCF function, indicating that ZYG-1 is regulated by a conserved mechanism. In C. elegans, similar to Drosophila and humans, we find that the Slimb/βTrCP homolog LIN-23 regulates ZYG-1 levels. In addition, we show that a second F-box protein, SEL-10, also contributes to ZYG-1 regulation. Co-depletion of LIN-23 and SEL-10 suggests these proteins function cooperatively. Because SEL-10 is the homolog of human FBW7, which is frequently mutated in cancer, our findings have implications for understanding tumorigenesis.
authors.affiliation: Department of Biology, The College of New Jersey, Ewing, NJ 08628, USA. peeln@tcnj.edu
authors.forename: Nina
authors.initials: N
authors.lastname: Peel
authors.forename: Michael
authors.initials: M
authors.lastname: Dougherty
authors.forename: Jacqueline
authors.initials: J
authors.lastname: Goeres
authors.forename: Yan
authors.initials: Y
authors.lastname: Liu
authors.forename: Kevin F
authors.initials: KF
authors.lastname: O'Connell
mesh_terms: D000818:Animals; D017173:Caenorhabditis elegans; D029742:Caenorhabditis elegans Proteins / Q000235:genetics / Q000378:metabolism*; D018797:Cell Cycle Proteins / Q000378:metabolism*; D002502:Centrioles / Q000235:genetics / Q000378:metabolism; D018385:Centrosome / Q000378:metabolism*; D044842:Cullin Proteins / Q000378:metabolism; D044783:F-Box Proteins / Q000378:metabolism*; D057809:HEK293 Cells; D006801:Humans; D008297:Male; D046988:Proteasome Endopeptidase Complex / Q000378:metabolism; D011494:Protein Kinases / Q000235:genetics / Q000378:metabolism*; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism; D034622:RNA Interference; D044843:SKP Cullin F-Box Protein Ligases / Q000378:metabolism
chemical_list: D029742:Caenorhabditis elegans Proteins; D018797:Cell Cycle Proteins; C100318:Cullin 1; D044842:Cullin Proteins; D044783:F-Box Proteins; C109554:SEL-10 protein, C elegans; C418507:lin-23 protein, C elegans; D044843:SKP Cullin F-Box Protein Ligases; C522506:SKR-1 protein, C elegans; D011494:Protein Kinases; C429649:zyg-1 protein, C elegans; D017346:Protein Serine-Threonine Kinases; D046988:Proteasome Endopeptidase Complex