By Sean Henahan, Access Excellence

Working with fruit flies, research geneticists discovered that a cellular signaling protein called MAD is responsible for switching genes on or off by binding directly to DNA, in effect telling  the cell to start or stop a specified task.

"We've shown that the MAD protein is a direct regulator of target gene transcription in response to a (specific) signal," said lead investigator Allen Laughon.

By revealing the terminus of the pathway by which cells send and receive messages, the new discovery forms the basis for the future treatment of  diseases like cancer, and provides a fundamental advance in understanding  a process that triggers decisive events in cells, he said.

The mapping of the communication pathways between cells is a fundamental quest in modern biology. Communication -- or miscommunication -- between cells is the basis for many diseases. For example, in humans it is believed that there are many layers of genes which act as a group to prevent cancer by blocking the inappropriate  proliferation of cells. But if these "tumor suppression genes" are defective, cells become blind to messages meant to ward off runaway cell proliferation. Cancer can be the result.

"As long as cells sense this information, they don't grow out of control," Laughon said.

"We've found a mechanism that is really important," said co-investigator Sean Carroll, a molecular biologist at the Howard Hughes Medical Institute at UW-Madison. "The universe of genes regulated by this pathway is very large. I would guess hundreds of genes."

"The missing link," explained Laughon, "has been how the signal switches genes on or off. This protein shuttles from the inner surface of the cell membrane right to the DNA, in one fell swoop."

While the discovery is not likely to lead immediately to breakthrough drugs, it could form the basis for new genetic- based treatments for disease, he added.

The research appears in the July 17, 1997 issue of  Nature.