Regulation of the Centrosome Cycle by Protein Degradation - The Centrosome - page 159

site via which SAS-4/CPAP binds tubulin dimers inhibits the formation of the
elongated centrioles induced by overexpression of the wild-type protein (Tang
et al. 2009 ).
CP110 caps the distal ends of centrioles (Kleylein-Sohn et al. 2007 ), where it
participates in restricting the length of the growing centriole and/or regulates
primary cilia generation. Depletion of CP110 leads to microtubule extensions
growing from both parental centrioles and procentrioles similar to those seen upon
SAS-4/CPAP overexpression (Schmidt et al. 2009 ; Tang et al. 2009 ). Additionally,
loss of CP110, or a protein that interacts with it, CEP97, induces the aberrant
formation of primary cilia in cycling cells, while in quiescent cells, enforced
expression of CP110 suppresses primary cilium assembly (Spektor et al. 2007 ).
Furthermore, depletion of the centriolar kinesin, Kif24, causes the loss of CP110
from mother centrioles, inducing cilia formation but not elongated centrioles per se
(Kobayashi and Dynlacht 2011 ). Through an unbiased screen, CP110 was iden-
tified as an interacting partner and substrate of Cyclin F (D'Angiolella et al. 2010 ).
Cyclin F, also called Fbxo1, is the founding member of the F-box protein family,
being the first protein in which the F-box motif was described (Bai et al. 1996 ).
CP110 and Cyclin F interact on centrioles in G2, with CP110 subsequently ub-
iquitylated by SCF Cyclin F and degraded (D'Angiolella et al. 2010 ). Depletion of
Cyclin F, or expression of a stable CP110 mutant unable to bind Cyclin F, leads to
both multipolar spindles and asymmetric, bipolar spindles with lagging chromo-
somes. If Cyclin F and CP110 were silenced together these phenotypes were
prevented (D'Angiolella et al. 2010 ). Potentially, Cyclin F also regulates CP110
levels to limit centrosome duplication to once per cell cycle, as depletion of CP110
prevents Plk4-induced centriole amplification (Kleylein-Sohn et al. 2007 ). How-
ever, CP110 levels may be controlled in mitosis so that cells enter the following
cell cycle with low CP110 abundance to allow primary cilium formation if the cell
enters quiescence.
9.4 Regulation of Centrosomes in Mitosis by Protein
Degradation
9.4.1 Centrosome Maturation and Disjunction
The onset of mitosis is accompanied by major changes in centrosome organization.
First of all, the PCM increases dramatically in size in a process known as cen-
trosome maturation. This includes a substantial increase in the amount of c-tubulin
and its associated partners leading to an overall increase in the microtubule
nucleation capacity of the centrosome (Khodjakov and Rieder 1999 ). Both Plk1
and Aurora A are required for centrosome maturation and, although the precise
pathways for this remain to be defined, it almost certainly involves regulation of
multiple centrosomal components (Haren et al. 2009 ; Kettenbach et al. 2011 ). At