CDC2-Cyclin B complex

In M phase, new phosphorylation of many proteins is observed that starts, in particular, from the CDC2-cyclin B complex. The phosphorylation mostly affects proteins involved in the reorganization of the cytoskeleton, the nuclear membrane and the formation of the spindle apparatus. As a consequence of phosphorylation events, inhibition of vesicular transport and general inhibition of transcription occur. 

Han SJ, Conti M. 2006. New pathways from PKA to the Cdc2/cyclin B complex in oocytes WeelB as a potential PKA substrate. Cell Cycle 5(3) 227-231. 

These toxins can influence the cell cycle by a complex series of direct and indirect actions on a variety of molecular targets by inhibiting protein phosphatases, hence altering the phosphorylation state of proteins involved in the control of the cell cycle. Exposine of mammalian cells to OA leads to hyperphosphorylation and activation of cyclin-dependent kinase 1-cyclin B complex (CDKl-cyc-lin B, called also M-phase-promoting factor, MPF or Cdc2-cyclin B), which leads the cells to G2/M transition and to a mitosis-like state, characterized by a premature chromosome condensation and break of the nuclear lamina. This event seems to depend mainly on the inhibition of protein phosphatase 2A, which is necessary to maintain the complex CDKl-cydin B in its inactive form. Nevertheless, inhibition of other phosphatases, such as protein phosphatases 4 and 5, could mediate. 

Mailer There are some stories coming out that Weel comes up in meiosis II. There might be low HI kinase activity, but there is still cyclin B present in a tyrosine-phosphorylated Cdc2 complex, and this might or might not be able to signal something about cell cycle phase. 

The best-characterized cyclin-dependent kinase in mammals is Cdkl, also named Cdc2. High-resolution structures are available of the inactive Cdkl without cyclin, and a partly active Cdkl-cyclin A complex. A schematic, simplified comparison of the essential features of the inactive and the active Cdk gives a clue as to how the enzyme is activated (Fig. 12.4a, b). Activation results from two events ... 

Entry into M phase is primarily determined by the activity of the cyclin B-CDC2 kinase complex, which is also called the mitosis-promoting factor, MPF. 

During S phase and G2 phase, the cyclin B-CDC2 complex accumulates in an inhibited state and is activated by the action of the Cdc25B/C enzymes at the G2/M transition. The active cyclin B-CDC2 complex phosphorylates numerous substrates and is inactivated by proteolysis only at the end of M phase and during Gj phase. 

Cyclins/cyclin-dependent kinases in higher eukaryotes - In higher eukaryotes, there are several "cyclin-dependent kinases" and a number of cyclins to associate with them. Each transition in the cell cycle appears to have a unique cyclin/kinase complex as its trigger. A simplified view of the roles of these proteins in mammalian cells is shown in Figure 28.16. The cyclin-dependent kinase CDK2 is involved in the entrance to S-phase, and cdc2, with cyclins A and B, regulates mitosis. 

Draetta, G., Luca, F., Westendorf, J., Brizuela, L., Ruderman, J., and Beach, D. (1989). cdc2 protein kinase is complexed with both cyclin A and B evidence for proteolytic inactivation of MPF. Cell 56 829-836. 

Entry into and the course of mitosis are primarily determined by the activity of the CDC2 kinase. The CDC2 kinase in the active form exists as a complex with cychn B and, together with the cyclin, forms the mitosis promoting factor, MPF. The activity of MPF oscillates in the cell cycle and is the triggering factor for entry of the cell into M phase. 

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