Cyclin B1 - Regulation

Regulation

Like all cyclins, levels of cyclin B1 oscillate over the course of the cell cycle. Just prior to mitosis, a large amount of cyclin B1 is present in the cell, but it is inactive due to phosphorylation of Cdk1 by the Wee1 kinase. The complex is activated by dephosphorylation by the phosphatase Cdc25. Cdc25 is always present in the cell but must be activated by phosphorylation. A possible trigger for activation is phosphorylation by cyclin A-Cdk, which functions before cyclin B1-Cdk in the cell cycle. Active Cdk1 is also capable of phosphorylating and activating Cdc25 and thus promote its own activation, resulting in a positive feedback loop. Once cyclin B1-Cdk1 is activated, it remains stably active for the rest of mitosis.

Another mechanism by which cyclin B1-Cdk1 activity is regulated is through subcellular localization. Before mitosis almost all cyclin B1 in the cell is located in the cytoplasm, but in late prophase it relocates to the nucleus. This is regulated by the phosphorylation of cyclin B1, in contrast to phosphorylation of Cdk1 regulating the activity of the complex. Phosphorylation of cyclin B1 causes it to be imported to the nucleus, and phosphorylation also prevents export from the nucleus by blocking the nuclear export signal. Cyclin B1 is phosphorylated by Polo kinase and Cdk1, again setting up a positive feedback loop that commits cyclin B1-Cdk1 to its fate.

At the end of mitosis, cyclin B1 is targeted for degradation by the APC through its APC localization sequence, permitting the cell to exit mitosis.