The correct segregation of DNA during cell division requires formation of a bipolar spindle, organized at each pole by a centrosome. 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. Ectopic expression of the kinase Plk4, which is required for centrosome duplication causes the formation of extra centrosomes, moreover aberrant Plk-4 expression levels are associated with cancer. Data from Drosophila and human cells suggests that Plk4 levels are regulated by the SCFslimb/bTrcp ubiquibin ligase and proteosomal degradation. In C. elegans it is unclear how levels of the functional homolog of Plk4, ZYG-1, are controlled. We show that levels of ZYG-1 are regulated by proteosomal degradation as inhibition of proteosome function leads to an increase in ZYG-1 protein levels. We further show that RNAi-mediated down-regulation of SCF components SKR-1/2 causes an increase in ZYG-1 levels, indicating that this complex is required to target ZYG-1 for degradation. We do not however find a role for the slimb/bTrcp homolog
lin-23 in ZYG-1 degradation. Surprisingly we find that the F-box protein SEL-10 is instead required to regulate ZYG-1 levels. Significantly, down-regulation of any of the SCFsel-10 components upregulates ZYG-1 activity sufficiently to restore centrosome duplication in a
zyg-1 hypomorphic mutant. Moreover, we find that components of the SCF complex show an overlapping pattern of localization with ZYG-1, consistent with their regulating ZYG-1 levels. Our results show that precise control of ZYG-1 levels is achieved through its proteosomal degradation directed by the SCFSEL-10 complex.