Researchers Discover Unusual Cell Survival Gene

Researchers at UC Santa Barbara have discovered a genetic switch that controls the process of "cell suicide" and protects cells from dying, they reported last month in the journal Nature.

The discovery may provide scientists with new means for identifying drugs that combat degenerative diseases, such as Lou Gehrig's disease (ALS), the destructive effects of strokes, heart diseases, autoimmune diseases, and cancer.

"Cell death is a key player in biology and medicine," said Joel Rothman, associate professor of molecular, cellular and developmental biology, and leader of the UCSB team. "Cells often commit suicide so that others may live."

Why would a cell kill itself off? "Programmed cell death is one of the first lines of defense against cancer and infection by invaders such as viruses," notes Rothman. "Ironically, the failure of a wayward cell to die can actually lead to death of the individual."

By killing itself off, a malignant or infected cell can prevent the disease from spreading. However, the throttle on cell death must be carefully set. "While death is a necessary part of our survival, too much cell death is disastrous," said Rothman. "That is what happens in degenerative diseases."

The gene identified by Rothman and UCSB postdoctoral researchers Tim Bloss and Eric Witze is called ICD-1 (inhibitor of cell death gene 1). It prevents normal cells from committing suicide. "We were startled to find that elimination of ICD-1 gene function causes lots of good cells to die by the same type of programmed suicide used to kill off harmful or defective cells, such as cancer cells," said Witze.

Though the aberrantly suicidal cells use some of the same cellular components to do themselves in, their path diverges somewhat from that used by cells whose normal fate is to commit suicide. This indicates that there are alternative avenues for the programmed death of cells in some circumstances, said Rothman.

The researchers discovered that the protein coded by the ICD-1 gene is usually found in a compartment within the cell called the mitochondrion. "That was a gratifying discovery: The ICD-1 protein works in the organelle that is pivotal for the programmed suicide of cells," said Bloss.