Infectious activation drives cell division

Mitosis is irreversible, only leading either to correct cell division or to genomically instable G1 cells, prone to cell death. The work of Dr. Rob Wolthuis was published in PLoS Biology, May issue.

Cyclin B1-Cdk1 activation is controlled in many ways, but once its activity rises above a certain level, further activation of Cyclin B1-Cdk1 is catalyzed by a positive-feedback loop. This triggers the start of mitosis. It is therefore critical to understand how Cyclin B1-Cdk1 can switch from an inactive to an active state. So far, no methods were available to measure how Cyclin B1–Cdk1 activity progresses in human cells over time.

Wolthuis his work combines activation measurements with a kinetic model to study how Cyclin B1-Cdk1 activity accumulates just before and during mitosis in human cells. He discovered that once Cyclin B1-Cdk1 activation is truly launched, it is bound to continue and will not lightly drop back again. Also different activity levels are required for initiation of, and progression through, mitosis.

On the basis of the findings, Wolthuis proposes that the successive Cyclin B1–Cdk1 activity levels by themselves may coordinate the progression through the distinct phases of the cell division process.