Biology

In the article written by Arne Lindqvist entitled Cyclin B-Cdk1 Activates Its Own Pump to Get into the Nucleus, the author points out that the transition to mitosis involves the importation of the kinase complex into the nucleus through the modification of the activity of the nucleocytoplasmic transport machinery.

According to the author, Cdk1 is complex because the cyclin B phosphorylates hundreds of target proteins that would promote the transition from the interphase to the mitosis (Lindqvist 197).  This leads to a dramatic cellular rearrangements requiring strict coordination of the cytoplasmic and nuclear events, especially since the cytoplasmic microtubules and the nuclear chromatin have to be reorganized first before the nuclear envelope breakdown for efficient capture of the chromosomes through the microtubles (Lindqvist 197).

According to Lindqvist,
Cyclin B-Cdk1 is responsible for these reorganizations, the mechanism by which its activity is regulated spatially and temporally has been the subject of intense investigation for two decades. (Lindqvist 197)    
How the nuclear translocation is regulated has been the subject of investigation in the past.  However, it has been concluded that the cyclin B-Cdk1 is first activated in the cytoplasmspecifically in the centrosomes (Lindqvist 197).  The regulation of the nuclear translocation starts by altering its interactions using import and export factors.  However, it remains to be unknown whether the Plk1 phosphorylates a residue, which can block the nuclear export.  

In a study done by Gavet and Pines, a novel biosensor was used, phosphorylated by cyclin B-Cdk1 in order to concurrently quantitate the kinase activity and the subcellular distribution patterns while the cell progresses into mitosis.  The cyclin B-Cdk1, upon phosphorylation, binds to the phosphoylated sequence, bringing the two fluorophores closer to one another.  The decreased distance leads to the increased efficiency of the Forster resonance energy transfer or FRET.  They found out that the biosensor in live cells was phosphorylated with similar kinetics in both the nucleus and the cytoplasm during mitotic entry (Lindqvist 197).  According to them, this is definitely surprising, since most of the cyclin B-Cdk1 is in the cytoplasm during the activation, which means that a large part of cyclin B-Cdk1 resides in the nucleus, as the activation continues in late phase.

Lindqvist observes that a mechanism must be at hand to ensure the distribution of active cyclin B-Cdk1 between nucleus and cytoplasm.  In the findings of Gavet and Pines, the nuclear translocation would depend on the dramatic increase in the nuclear import of cyclin B and not on the decrease in nuclear export.  Lindqvist adds that Plk1 does not affect the rate of cyclin B-Cdk1 nuclear translocation but, rather, cannot process through the phosphorylation of the previously identified residues in cyclin B.  According to the source, Gavet and Pines found that cyclin B-Cdk1 activity itself directly regulates nuclear translocation by dramatically increasing its own nuclear import (Lindqvist 198).

There are three implications with regards to this finding first, that the cyclin B-Cdk1 is first activated in the cytoplasm second, that it is not possible to restrict active pool of cyclin B-Cdk1 to the cytoplasm, since the active cyclin B-Cdk1 will promote its own translocation third and final, that the coupling cyclin B-Cdk1 activity to its own nuclear import is an elegant mechanism that ensures the activation of the B-Cdk1 throughout the cell (Lindqvist 198).  Therefore, all these indicate that there is a possibility that other proteins also translocate at the same time as the cyclin B-Cdk1.  This directs cellular rearrangements through the redistribution of proteins during the mitotic entry.