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protein degradation pathways. In addition, proteasome inhibitors lead to an
accumulation of ubiquitylated centrosomal proteins including c-Tubulin, TUB-
GCP4, NEDD1, Ninein, pericentrin, dynactin, and PCM-1 (Didier et al. 2008 ).
This accumulation is independent of microtubules, suggesting that the centrosome
is the normal site for degradation of these proteins. The accumulation of these non-
degraded proteins reduces the ability of centrosomes to form microtubule asters,
suggesting that proteasome activity regulates the turnover of centrosome proteins
in order to regulate centrosome homeostasis, and may further suggest a potential
role in centrosome maturation.
Moreover, noncentrosomal degradation events are also relevant to centrosome
homeostasis. Emi1 is an APC/C inhibitor that keeps the APC/C inactive during S
and G2, but must be inactivated for cells to enter mitosis. In mitosis Emi1 is
phosphorylated by Cdk1, after which it can be targeted by bTrCP/Slimb for SCF-
dependent degradation (Margottin-Goguet et al. 2003 ). Expression of nonde-
gradable Emi1 causes delayed activation of the APC/C and prolonged stabilization
of APC/C substrates, which leads to metaphase arrest followed by mitotic catas-
trophe and centrosome amplification (Margottin-Goguet et al. 2003 ). Although
Emi does not directly regulate either a centrosomal degradation pathway or sub-
strate, such non-centrosomal events can nonetheless have a major impact on
centrosome homeostasis, and there are likely to be other non-centrosomal events
that more directly impact centrosome biology.
8.13 Conclusions and Prospective
As discussed above, proteolysis controls centrosome duplication and function at
many levels and through many pathways. While the role of proteolysis in MTOC
assembly and function appears to be conserved throughout eukaryotes, there are
clearly mysteries yet to be solved. For example, no Rpt4p substrate involved in SPB
duplication in yeast has been identified, so the degree to which proteolysis controls
the function of non-centriole containing MTOCs remains unclear, and if proteolysis
plays a major role in SPB duplication and/or function that role remains to be
identified. While this review is intended to be as inclusive as possible, there are
certain to be other degradation pathways and events not discussed here that are
relevant to centrosomes and/or SPBs. While some may be known but regrettably
overlooked here, there are likely more that are not yet known. It seems likely that the
story of centrosomal degradation has not completely unfolded, and that much about
the control of centrosome biology by regulated protein destruction remains to be
uncovered. In fact, the observation in worms that PP2A controls the levels of Sas-5
in a proteasome-dependent manner (Song et al. 2011 ) suggests that regulated deg-
radation may be a common feature of centriole assembly factors, even if their
degradation has not yet been studied. Interestingly, despite initial searches that
suggested there was no human ortholog of Sas-5, the STIL protein is likely to be the
human Sas5 ortholog based on its similarity to the fly Ana2 (Stevens et al. 2010 ),
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