The group headed by Vincent Archambault at IRIC has made an important discovery about cell division that has just been published in the prestigious journal Nature Communications. Cell division is a fascinating process. It is controlled by molecular mechanisms involving proteins that have been largely conserved between species through evolution. The Archambault lab uses the fruit fly Drosophila as a powerful model system to decipher cell division at the molecular level. This knowledge helps better understand cancers.

Postdoctoral fellow David Kachaner and colleagues have discovered a new mechanism that is crucial for the cells’ initiation of mitosis, the physical separation of chromosomes leading to cell division. The Polo kinase is an enzyme that adds phosphate groups to several target proteins to modify their activities as the cell progresses trough cell division. Polo is needed for mitosis, but scientists do not completely understand how Polo functions. However, they know that while its activity is required in the cell’s nucleus as the cell enters mitosis, Polo can only be activated outside the nucleus, in the cytoplasm. How Polo’s activation is coupled to its entry in the nucleus was a mystery.

Dr Kachaner and colleagues found that activation of Polo kinase by addition of a phosphate group near its catalytic site also induces a structural change in Polo which exposes a nuclear localization signal (NLS), recognized by proteins that mediate nuclear import (Figure). Once in the nucleus, Polo activates the enzyme Cdc25 and promotes its relocalization from the nucleus to the cytoplasm. There, Cdc25 can activate CDK1, another crucial kinase required to trigger multiple aspects of mitosis. Disruptions in these mechanisms lead to severe defects in cell division and result in failures of flies to develop normally.

All enzymes involved in the mechanism discovered also exist in humans. Moreover, the Polo kinase (Polo-like kinase 1 in humans) is the target of cancer drugs currently in clinical trials, but these molecules are not optimal. The new findings may help develop better drugs targeting Polo or the other proteins with which it functions.

To learn more, access the article: http://rdcu.be/y7Df

 

 
 
Figure. The newly discovered mechanism coupling Polo activation and localization. The Polo enzyme is inactive in the cell cytoplasm. When activated by addition of a phosphate (yellow), Polo exposes an NLS motif (red) that sends it to the cell nucleus. There, Polo activates Cdc25, which in turn activates CDK1, the enzyme that triggers mitosis.

 

Mitoses in a Drosophila embryo

Blue: chromosomes; Green: microtubules; Red: centrosomes and nuclear envelopes.