Cyclin B-Cdk1 activates its own pump to get into the nucleus

Abstract

The transition to mitosis requires extensive nuclear and cytoplasmic rearrangements that must be spatially and temporally coordinated. In this issue, Gavet and Pines (2010a. J. Cell Biol. doi:10.1083/jcb.200909144) report on a simple yet elegant mechanism as to how this is achieved. By monitoring the activity of cyclin B-Cdk1 in real time, the authors show that concomitant with its activation in the cytoplasm, the kinase complex is rapidly imported into the nucleus by modifying the activity of the nucleocytoplasmic transport machinery. Thus, cyclin B-Cdk1 activates its own pump to get into the nucleus.

Figure 1.

The coordination problem. Condensation of nuclear chromatin (blue), maturation and separation of cytoplasmic centrosomes (green), and altered dynamics of cytoplasmic microtubules (red) need to be synchronized in prophase to ensure timely assembly of a bipolar mitotic spindle once the nuclear envelope (yellow) breaks down.

Figure 2.

Cyclin B–Cdk1 activity is similar in the nucleus and in the cytoplasm. The kinetics of phosphorylation of a nuclear and a cytoplasmic cyclin B–Cdk1 target (color gradient) is similar despite large differences in the nuclear and cytoplasmic concentrations of cyclin B–Cdk1 (white lines) during mitotic entry.

Figure 3.

Coupling between cyclin B–Cdk1 activity and nuclear translocation ensures spatial coordination of early mitotic events. Cyclin B–Cdk1 activity causes a general change in the transport machinery that triggers cyclin B–Cdk1 nuclear import. Cyclin B–Cdk1-dependent changes of the transport machinery may also lead to coordinated redistribution of other mitotic regulators, e.g., by enabling nuclear microtubule regulators access to cytoplasmic microtubules.