Polo Takes The Bait

Matrimony (Mtrm), a seemingly obscure gene in the female fruit fly that is only active in cells that will become eggs, led Investigator R. Scott Hawley’s team to the discovery of an atypical protein that lures, traps, and inactivates the powerful Polo kinase. Polo is widely considered the master regulator of cell division, and its human homolog, Polo-like kinase-1 (Plk1), is misregulated in many types of cancer.

The Hawley lab discovered the Matrimony gene in 2003 and over time learned that Mtrm was a critical player in the cell divisions that occur as an egg is being made. In their latest study, Matrimony emerged as a rare example of a protein that can stably bind (and turn off) Polo kinase. It attracts the Polo kinase with three phosphorylated amino acids that resemble Polo’s favored binding sites. As soon as Polo takes the bait, the other end of Matrimony wraps around Polo and represses its function.

Hawley hopes that this highly selective kinase trap might give drug developers, who are working to inhibit Polo’s crucial role in driving the multiplication of cancer cells, a new method to inactivate Polo without blocking other vital kinases in normal cells. “It provides some real therapeutic possibilities because Polo is misregulated
in so many types of cancer,” says the study’s lead author Amanda Bonner, a former research technician in Hawley’s lab. “To find something small and specific to Polo that doesn’t interact with anything else is pretty exciting.”

The study was published in the March 23, 2013, edition of the Proceedings of the National Academy of Science and picked as an “Editor’s choice” in the April 5 issue of Science.