The events of the cell division cycle can be summarized as follows: the G1 cyclins prepare the chromosomes for replication via interactions with corresponding CDKs. A consequent increase in S-phase promoting factors prepares the cell to enter S-phase and duplicate its DNA. As replication continues, one of the cyclins shared by both the G1- and the S-phase CDKs, cyclin E, is destroyed and an increase in M-phase cyclins (cyclins A, B) ensues. M-phase-promoting factors such as cyclins A and B and CDK1 lead to mitotic spindle assembly, breakdown of the nuclear envelope, and chromatin condensation, each of which takes place prior to mitotic anaphase. At this point, the MPF (CDK1/ cyclin B) promotes APC assembly which induces sister chromatid separation and movement to the poles. In order for cells to continue cyclin, phase-specific cyclins must be degraded by the ubiquitin proteasome pathway which targets proteins for destruction by covalent bonding of small ubiquitin molecules permitting their recognition by the protea-some. The INK4 and CIP/KIP families of CDKIs add another level of regulation to the cell cycle. Inhibition of CDK activation through the administration of small-molecule inhibitors is showing promise as a clinical therapeutic strategy through the ability to interrupt CDK enzymatic activity either directly or indirectly.


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PLATE 9.2 (Fig. 9.2)

cdc25A phosphatase PLATE 9.3 (Fig. 9.3)

PLATE 9.4 (Fig. 9.4)
PLATE 9.6 (Fig. 9.6)
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