Regulation of the Centrosome Cycle by Protein Degradation - The Centrosome - page 151

Chapter 9
Regulation of the Centrosome Cycle
by Protein Degradation

Suzanna L. Prosser and Andrew M. Fry

Abstract 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 dupli-
cation 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 centro-
some cycle will be considered in this chapter.

9.1 Introduction: Protein Degradation in Cell Cycle Control

The cell cycle describes a sequential order of events that culminate in cell division.
These events are driven by oscillations in the level of cyclin-dependent kinase (Cdk)
activity (Nurse 2000 ). However, phosphorylation is a rapidly reversible form of

S. L. Prosser A. M. Fry ( )

Department of Biochemistry, University of Leicester,
Lancaster Road, Leicester LE1 9HN, UK
e-mail: [e-mail]

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