Regulation of the Centrosome Cycle by Protein Degradation - The Centrosome - page 154

Fig. 9.1 APC/C and SCF activity during the centrosome cycle. The cell begins the centrosome
cycle in G1 with one centrosome, consisting of a pair of centrioles loosely tethered at their proximal
ends by a proteinaceous linker (black strands). The older, mother, centriole (black cylinder)is
structurally distinct from the younger, daughter, centriole (brown cylinder) as it has additional
appendages at its distal end; it is also associated with the bulk of the PCM (green). As the cell
progresses into S-phase, centrosome duplication commences with the appearance of procentrioles
(pink cylinders) at the proximal ends of the existing centrioles, a positioning that dictates the tight
orthogonal arrangement of an engaged centriole pair, and which is maintained until late mitosis. The
procentrioles elongate as the cell moves through G2, reaching full length at mitosis. At the G2/M
transition, the linker between the original mother and daughter is lost, allowing the two centrosomes
to move apart and form the poles of the bipolar mitotic spindle. At anaphase, centriole
disengagement occurs, thereby licensing duplication in the subsequent cell cycle. Many key
centrosomal proteins are regulated by protein degradation to ensure the fidelity of the centrosome
cycle. The APC/C Cdc20 is active from early mitosis until anaphase, when the APC/C Cdh1 become
active until late G1. The SCF is active throughout the cell cycle, being directed to its targets via their
phosphorylation and subsequent recognition by specific F-box proteins
9.3 Regulation of Centriole Duplication by Protein
Degradation
9.3.1 Regulation of Centriole Biogenesis
Early studies into the molecular control of centriole duplication revealed an
essential requirement for Cdk2 (Hinchcliffe et al. 1999 ; Matsumoto et al. 1999 ;
Lacey et al. 1999 ; Meraldi et al. 1999 ). This important discovery provided the first
clue for how cells ensure that when they enter mitosis they will have duplicated
both their DNA and centrosome. Cdk2 is activated at the G1/S transition through