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The SCF^Slimb ubiquitin ligase regulates Plk4/Sak levels to block centriole reduplication

¹ Department of Biology, ² Carolina Center for Genome Sciences, and ³ Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599

Correspondence to Stephen L. Rogers: srogers{at}bio.unc.edu

Restricting centriole duplication to once per cell cycle is critical for chromosome segregation and genomic stability, but the mechanisms underlying this block to reduplication are unclear. Genetic analyses have suggested an involvement for Skp/Cullin/F box (SCF)-class ubiquitin ligases in this process. In this study, we describe a mechanism to prevent centriole reduplication in Drosophila melanogaster whereby the SCF E3 ubiquitin ligase in complex with the F-box protein Slimb mediates proteolytic degradation of the centrosomal regulatory kinase Plk4. We identified SCF^Slimb as a regulator of centriole duplication via an RNA interference (RNAi) screen of Cullin-based ubiquitin ligases. We found that Plk4 binds to Slimb and is an SCF^Slimb target. Both Slimb and Plk4 localize to centrioles, with Plk4 levels highest at mitosis and absent during S phase. Using a Plk4 Slimb-binding mutant and Slimb RNAi, we show that Slimb regulates Plk4 localization to centrioles during interphase, thus regulating centriole number and ensuring the block to centriole reduplication.

Abbreviations used in this paper: CLB, cell lysis buffer; D-PLP, Drosophila pericentrin-like protein; dsRNA, double-stranded RNA; HTM, high-throughput microscopy; HU, hydroxyurea; Nlp, nucleophosmin; PCM, pericentriolar material; SAS-6p, SAS-6 promoter; SBM, Slimb-binding mutant; SCF, Skp/Cullin/F box.

© 2009 Rogers et al.
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This article has been cited by other articles:

• Korzeniewski, N., Zheng, L., Cuevas, R., Parry, J., Chatterjee, P., Anderton, B., Duensing, A., Munger, K., Duensing, S. (2009). Cullin 1 Functions as a Centrosomal Suppressor of Centriole Multiplication by Regulating Polo-like Kinase 4 Protein Levels. Cancer Res. 69: 6668-6675 [Abstract] [Full Text]  
• Leslie, M. (2009). Birth control for centrioles. JCB 184: 186-186 [Full Text]  

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