The SCF Slimb ubiquitin ligase regulates Plk4/Sak levels to block centriole reduplication.
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.
Rogers
Gregory C
GC
Department of Biology, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA.
Rusan
Nasser M
NM
Roberts
David M
DM
Peifer
Mark
M
Rogers
Stephen L
SL
D000818:Animals; D002453:Cell Cycle; D018797:Cell Cycle Proteins / Q000032:analysis / Q000378:metabolism*; D002478:Cells, Cultured; D002502:Centrioles / Q000378:metabolism / Q000502:physiology*; D015536:Down-Regulation; D004330:Drosophila / Q000378:metabolism; D029721:Drosophila Proteins / Q000032:analysis / Q000378:metabolism*; D017346:Protein Serine-Threonine Kinases / Q000235:genetics / Q000378:metabolism*; D034622:RNA Interference; D044843:SKP Cullin F-Box Protein Ligases / Q000032:analysis / Q000378:metabolism*; D044767:Ubiquitin-Protein Ligases / Q000032:analysis / Q000378:metabolism*; D054875:Ubiquitination
D018797:Cell Cycle Proteins; D029721:Drosophila Proteins; C110233:slmb protein, Drosophila; D044843:SKP Cullin F-Box Protein Ligases; D044767:Ubiquitin-Protein Ligases; D017346:Protein Serine-Threonine Kinases; C522064:Sak protein, Drosophila