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The SCF-FBXW5 E3-ubiquitin ligase is regulated by PLK4 and targets HsSAS-6 to control centrosome duplication.
- Source :
-
Nature Cell Biology . Aug2011, Vol. 13 Issue 8, p1004-1009. 6p. 1 Color Photograph, 1 Black and White Photograph, 1 Diagram, 8 Graphs. - Publication Year :
- 2011
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Abstract
- Deregulated centrosome duplication can result in genetic instability and contribute to tumorigenesis. Here, we show that centrosome duplication is regulated by the activity of an E3-ubiquitin ligase that employs the F-box protein FBXW5 (ref. ) as its targeting subunit. Depletion of endogenous FBXW5 or overexpression of an F-box-deleted mutant version results in centrosome overduplication and formation of multipolar spindles. We identify the centriolar protein HsSAS-6 (refs , ) as a critical substrate of the SCF-FBXW5 complex. FBXW5 binds HsSAS-6 and promotes its ubiquitylation in vivo. The activity of SCF-FBXW5 is in turn negatively regulated by Polo-like kinase 4 (PLK4), which phosphorylates FBXW5 at Ser 151 to suppress its ability to ubiquitylate HsSAS-6. FBXW5 is a cell-cycle-regulated protein with expression levels peaking at the G1/S transition. We show that FBXW5 levels are controlled by the anaphase-promoting (APC/C) complex, which targets FBXW5 for degradation during mitosis and G1, thereby helping to reset the centrosome duplication machinery. In summary, we show that a cell-cycle-regulated SCF complex is regulated by the kinase PLK4, and that this in turn restricts centrosome re-duplication through degradation of the centriolar protein HsSAS-6. [ABSTRACT FROM AUTHOR]
Details
- Language :
- English
- ISSN :
- 14657392
- Volume :
- 13
- Issue :
- 8
- Database :
- Academic Search Index
- Journal :
- Nature Cell Biology
- Publication Type :
- Academic Journal
- Accession number :
- 63554665
- Full Text :
- https://doi.org/10.1038/ncb2282