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  4. The SCF-FBXW5 E3-ubiquitin ligase is regulated by PLK4 and targets HsSAS-6 to control centrosome duplication
 
research article

The SCF-FBXW5 E3-ubiquitin ligase is regulated by PLK4 and targets HsSAS-6 to control centrosome duplication

Puklowski, Anja
•
Homsi, Yahya
•
Keller, Debora  
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2011
Nature Cell Biology

Deregulated centrosome duplication can result in genetic instability and contribute to tumorigenesis(1,2). Here, we show that centrosome duplication is regulated by the activity of an E3-ubiquitin ligase that employs the F-box protein FBXW5 (ref. 3) as its targeting subunit. Depletion of endogenous FBXW5 or over expression of an F-box-deleted mutant version results in centrosome overduplication and formation of multipolar spindles. We identify the centriolar protein HsSAS-6 (refs 4,5) 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.

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Type
research article
DOI
10.1038/ncb2282
Web of Science ID

WOS:000293373700020

Author(s)
Puklowski, Anja
Homsi, Yahya
Keller, Debora  
May, Martin
Chauhan, Sangeeta
Kossatz, Uta
Gruenwald, Viktor
Kubicka, Stefan
Pich, Andreas
Manns, Michael P.
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Date Issued

2011

Publisher

Nature Publishing Group

Published in
Nature Cell Biology
Volume

13

Issue

8

Start page

1004

End page

U291

Subjects

Cell-Cycle

•

C-Elegans

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Centriole

•

Protein

•

Suppressor

•

Degradation

•

Family

•

Box

Editorial or Peer reviewed

REVIEWED

Written at

EPFL

EPFL units
UPGON  
Available on Infoscience
December 16, 2011
Use this identifier to reference this record
https://infoscience.epfl.ch/handle/20.500.14299/73748
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