They noticed that when an O-GlcNAc molecule was located near a phosphate site, or at the same site, it prevented the phosphate from attaching. The proteins involved in cell division weren't phosphorylated and activated until O-GlcNAc detached.
"I think of phosphorylation as a micro-switch that regulates the circuitry of cell division, and O-GlcNAcylation as the safety switch that regulates the microswitches," says Gerald Hart, Ph.D., the DeLamar Professor and director of biological chemistry at the Johns Hopkins School of Medicine.
Using a standard human cell line (HeLa cells), the scientists discovered abnormalities when they disrupted the cell division process by adding extra O-GlcNAc. Although the cell's chromosome-containing nuclei divided normally, the cells themselves didn't divide, resulting in too many nuclei per cell a condition known as polyploidy that's exhibited by many cancer cells.
The researchers not only mapped O-GlcNAc and phosphorylation sites but also measured changes in the cell division machinery, because, Hart says, the chemical changes act more like "dimmer" switches, than simple on/off ones.
As important as the discovery is to a deeper understanding of cell division, Hart says, this extensive cross talk between O-GlcNAc and phosphorylation is paradigm-shifting in terms of signaling. Signaling is how a cell perceives its environment, and how it regulates its machinery in response to stimuli. The new sugar switches reveal that the cellular circuitry is much more complex than previously thought, he adds.
|Contact: Maryalice Yakutchik|
Johns Hopkins Medical Institutions