Once the cell has duplicated its DNA in S phase, the next step is to generate the mitotic spindle, disassemble the nuclear envelope, condense the chromosomes and align each pair of sister chromatids appropriately.
The transition is controlled by CDK-CYCB kinase activity. During G2 , the amount of CYCB (cyclin B) increases and becomes associated with both cyclin-dependent protein
Inhibitory phosphorylation by WEE-kinase
Cyclin-dependent * kinase
Binding of inhibitory KR proteins
Activating phosphorylation CAK-kinase
Figure 10.3 Regulation of cyclin-dependent kinase activity.
kinases A (CDKA) and B (CDKB). However, both KRP proteins and inhibitory phosphorylation by WEE kinases render the complex inactive. It is thought that specific protein phosphates reverse the inhibitory protein phophorylation to allow entry into M phase. Thus, cyclin-dependent kinases regulate progression through the cell cycle by reversible phosphorylation.
Progression through mitosis involves the association of the CDK complexes with microtubule and chromatin proteins. CDK activity is therefore likely to play an important part in microtubule dynamics and stability. The kinesins are a class of microtubule-associated proteins that have a motor domain which allows movement along the micro-tubules. They have key roles in spindle formulation and cell plate dynamics (Vanstraelen et al., 2006). At least 23 kinesins have been implicated in mitosis using the energy of ATP to control microtubule organisation, polymerisation, depolymerisation and chromosome movement. The 23 kinesins are up-regulated during mitosis and their proposed involvement in spindle dynamics is reviewed by Vanstraelen et al. (2006).
In essence, progression through the cell cycle requires successive phosphorlyation events and the removal of regulatory and structural proteins by proteolytic degradation.
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