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

Gregory C. Rogers, Nasser M. Rusan, David M. Roberts, Mark Peifer, Stephen L. Rogers

Research output: Contribution to journalArticle

151 Citations (Scopus)

Abstract

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 identifi ed 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.

Original languageEnglish (US)
Pages (from-to)225-229
Number of pages5
JournalJournal of Cell Biology
Volume184
Issue number2
DOIs
StatePublished - Jan 26 2009
Externally publishedYes

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Cullin Proteins
Centrioles
Ligases
Ubiquitin
RNA Interference
F-Box Proteins
Chromosomal Instability
Chromosome Segregation
Ubiquitin-Protein Ligases
Genomic Instability
Interphase
Drosophila melanogaster
S Phase
Mitosis
Cell Cycle
Phosphotransferases

ASJC Scopus subject areas

  • Cell Biology
  • Medicine(all)

Cite this

The SCF Slimb ubiquitin ligase regulates Plk4/Sak levels to block centriole reduplication. / Rogers, Gregory C.; Rusan, Nasser M.; Roberts, David M.; Peifer, Mark; Rogers, Stephen L.

In: Journal of Cell Biology, Vol. 184, No. 2, 26.01.2009, p. 225-229.

Research output: Contribution to journalArticle

Rogers, Gregory C. ; Rusan, Nasser M. ; Roberts, David M. ; Peifer, Mark ; Rogers, Stephen L. / The SCF Slimb ubiquitin ligase regulates Plk4/Sak levels to block centriole reduplication. In: Journal of Cell Biology. 2009 ; Vol. 184, No. 2. pp. 225-229.
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