Regulation of the Centrosome Cycle by Protein Degradation
Irreversible protein destruction is a key regulatory mechanism controlling progression through the cell cycle. This is orchestrated by ubiquitin ligases, the two most prominent of which in the cell cycle are the anaphase promoting complex/cyclosome (APC/C) and the Skp1/Cullin/F-box (SCF) protein. Through targeting specific proteins for timely degradation, these complexes not only ensure accurate control of the cell cycle, but also ensure precise regulation of the centrosome duplication cycle. Disruption of the centrosome cycle can lead to formation of aberrant or supernumerary centrosomes that in turn contribute to cell division errors and genetic instability. Recent progress has revealed that protein degradation mechanisms are central to many aspects of centriole biogenesis. By strictly regulating the abundance of core centriole assembly proteins, the number of new centrioles formed within each cell cycle is tightly controlled. Moreover, protein destruction is equally important in ensuring that centrioles of the correct length are formed, while licensing of centriole duplication, which occurs during mitosis, is also controlled by protein degradation. The major ubiquitin-mediated degradation events that ensure fidelity of the centrosome cycle will be considered in this chapter.
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