Johns Hopkins scientists have discovered that a deceptively simple sugar is in fact a critical regulator of cells' natural life cycle.
The discovery reveals that, when disturbed, this process could contribute to cancer or other diseases by failing to properly control the steps and timing of cell division, the researchers say. The findings are described in the Sept. 23 issue of the Journal of Biological Chemistry, available online now.
The sugar, known as O-GlcNAc (pronounced oh-GLUCK-nack), is used inside cells to modify proteins, turning the proteins off or on, helping or preventing their interactions with other proteins, keeping them from destruction or allowing their destruction. The comings and goings of the sugar on proteins seem to be important controllers of cell division, say the researchers.
"The dogma for decades has been that the cycle of cell division is controlled by the appearance and disappearance of certain proteins called cyclins, but experiments have shown that you can knock out any of these and still get perfectly normal cell division," says the study's first author, Chad Slawson, Ph.D., a postdoctoral fellow in biological chemistry in Johns Hopkins' Institute for Basic Biomedical Sciences. "In contrast, our experiments show that by increasing or decreasing the amount of sugar attached to proteins, the cell cycle is disrupted and isn't salvageable unless O-GlcNAc levels are fixed."
In experiments with human cells and mouse cells, Slawson and his colleagues showed that preventing a cell from removing the sugar from proteins causes the cell to copy its genetic material and make new nuclei, but to fail to divide in two. The end result is cells with more than one nucleus -- a situation fairly common in cancer cells.
"Cells with more than one nucleus can survive, but they are dysregulated -- things just don't go right," says Slawson. "The longer they survive, the worse it gets."
On the other hand, cells th
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Source:Johns Hopkins Medical Institutions
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