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they involved in phosphorylation or ubiquitination, and ensures that each centriole
duplicates only once per cell cycle. Second, centriole biogenesis appears to be
exquisitely sensitive to the expression level of centriole assembly factors. The extent
of transcription, translation, and degradation of these proteins must be in perfect
balance to ensure ''copy number control'', i.e., that only a single procentriole is
nucleated by each parental centriole (Nigg
2007
). Third, localization is critically
important with the centrosome acting as the primary site of localization for both
substrates for degradation and components of the ubiquitylation system, including
E2 and E3 enzymes. This may also provide a mechanism for localized degradation
that can be temporally, as well as spatially, separated from degradation throughout
the rest of the cell (Mathe et al.
2004
). Hence, the centrosome is not only under the
control of degradation processes but can itself regulate such events.
Considerable advances have clearly been made in recent years into the molecular
regulation of the centrosome duplication cycle and the role that protein degradation has
in this process. However, much still remains to be learned; for example, what Plk4
phosphorylates in mitosis to regulate centriole assembly, what regulates the recogni-
tion of SAS-6 by Fbxw5, what controls expression of SAS-5, and what are the targets of
separase and Plk1 that regulate centriole disengagement. With the current rapid rate of
progress, one can expect answers to these and other related questions in the near future.
Acknowledgments We are grateful to all members of our laboratory for useful discussion and to
The Wellcome Trust, the Biotechnology and Biological Sciences Research Council, the Asso-
ciation for International Cancer Research and Cancer Research, UK for supporting our research.
AMF is a member of the Leicester Experimental Cancer Medicine Centre.
References
Ahmed AA et al (2010) SIK2 is a centrosome kinase required for bipolar mitotic spindle formation
that provides a potential target for therapy in ovarian cancer. Cancer Cell 18:109-121
Bahe S, Stierhof YD, Wilkinson CJ, Leiss F, Nigg EA (2005) Rootletin forms centriole-
associated filaments and functions in centrosome cohesion. J Cell Biol 171:27-33
Bai C et al (1996) SKP1 connects cell cycle regulators to the ubiquitin proteolysis machinery
through a novel motif, the F-box. Cell 86:263-274
Bettencourt-Dias M, Glover DM (2007) Centrosome biogenesis and function: centrosomics
brings new understanding. Nat Rev Mol Cell Biol 8:451-463
Bettencourt-Dias M et al (2005) SAK/PLK4 is required for centriole duplication and flagella
development. Curr Biol 15:2199-2207
Brownlee CW, Klebba JE, Buster DW, Rogers GC (2011) The Protein Phosphatase 2A regulatory
subunit Twins stabilizes Plk4 to induce centriole amplification. J Cell Biol 195:231-243
Cardozo T, Pagano M (2004) The SCF ubiquitin ligase: insights into a molecular machine. Nat
Rev Mol Cell Biol 5:739-751
Casenghi M et al (2003) Polo-like kinase 1 regulates Nlp, a centrosome protein involved in
microtubule nucleation. Dev Cell 5:113-125
Cormier A et al (2009) The PN2-3 domain of centrosomal P4.1-associated protein implements a
novel mechanism for tubulin sequestration. J Biol Chem 284:6909-6917
Cunha-Ferreira I et al (2009) The SCF/Slimb ubiquitin ligase limits centrosome amplification
through degradation of SAK/PLK4. Curr Biol 19:43-49
