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Cell Survival Signal Sighted

Study identifies molecules that pull cells back from the brink of death

THURSDAY, Feb. 7, 2002 (HealthDayNews) -- New research has identified the chemical pathway that can talk a suicidal cell off the molecular equivalent of a window ledge.

Scientists have found that a series of proteins suppress the sequence of events leading to natural cell death. Although previous studies have shed light on the factors that control this cell death, which is called apoptosis, this new research is the first to find the molecular signals that tell certain cells to survive.

Kristin White, an expert on apoptosis at Harvard University, says the findings, which appear in the current issue of the journal Developmental Cell, answer critical questions about how these mechanisms work in a living system.

Andreas Bergmann, who is now an assistant professor at the University of Texas M.D. Anderson Cancer Center in Houston, looked at developing fruit flies to see how brain cells called neurons send survival messages to neighboring brain cells called glial cells.

During development, billions of each type of cells are created. Most succumb to apoptosis because they've fulfilled their functions, are incorrectly located or are simply excessive. It is known that proteins aptly called grim, rpr and head involution defective (HID), form part of the apoptosis pathway, unleashing other proteins called caspases that kill cells.

What was less clear is what signals the small fraction of cells that survive into the mature brain to live.

"There must be mechanisms which regulate which cells continue to live and which . . . die," Bergmann says.

Through their research, Bergmann and his colleagues at Rockefeller University in New York found a chemical called SPITZ binds to a specialized receptor called EGF. This turns on a chemical pathway known as RAS/MAPK, which puts a chokehold on the HID protein and prevents the release of cell-killing caspases.

"There is a cell death program inside these cells, and this cell death program has to be inactivated, otherwise these cells die," says Bergmann. "What the survival [chemicals] are doing is triggering a signaling pathway which signals survival to the glial cells and inactivates the cell death program inside."

White, a principal investigator at Harvard's Cutaneous Biology Research Center, says that while a great deal of apoptosis research has been done in studies of cell cultures, this new research looks at the role of apoptosis in the whole animal.

Cell cultures have shown that chemical signals through the RAS/MAPK pathways are often required to keep cells alive, she says.

"What we didn't know was how that's important during development, and where that signal's coming from, and what are the cells receiving it," says White. "Those are the things they've defined in this paper."

The RAS/MAPK pathway has already been studied in cancer, where it's known to prevent the body from killing off harmful cells. Bergmann says these findings could shed light on new ways to target cancers.

White adds future studies could look at how this pathway functions elsewhere in the growing organism, for example, in the developing eye.

What To Do: Find out more about apoptosis from Cells Alive!, the WellnessWeb or the National Institutes of Health.

SOURCES: Interviews with Andreas Bergmann, Ph.D., assistant professor, department of biochemistry & molecular biology, University of Texas M.D. Anderson Cancer Center, Houston; Kristin White, Ph.D., principal investigator, Cutaneous Biology Research Center, department of cell biology, Massachusetts General Hospital East, Charlestown, Mass.; Feb. 1, 2002, Developmental Cell.
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