ATLANTA -- An enzyme viewed as an executioner, because it can push cells to commit suicide, may actually short circuit a second form of cell death, researchers at Emory University School of Medicine have discovered.
The finding could shift drug discovery efforts, by leading scientists to rethink how proposed anti-cancer and anti-inflammatory drugs that target the enzyme, called caspase 8, are supposed to work. The results are described in this week's Nature.
Caspase 8 has been described as "the killer you can't live without." This enzyme plays a key role in apoptosis, a form of cellular suicide important for the development of all multicellular organisms, and in defense against viral infections. Mice lacking caspase 8 die before birth, because their blood vessels and blood-forming stem cells fail to develop properly. In the Nature paper, Emory researchers show that mice without caspase 8 develop normally if they also lack another enzyme called RIP3.
"The surprising aspect is that caspase 8 appears to have two functions: one that initiates apoptosis and a second that restrains an independent programmed death pathway," says senior author Ed Mocarski, PhD, Robert W. Woodruff Professor of Microbiology and Immunology at Emory Vaccine Center and Emory University School of Medicine.
Graduate student William Kaiser, in Emory's Microbiology and Molecular Genetics program, is the first author of the paper. Other Emory authors include Tamara Caspary, PhD, assistant professor of human genetics, as well as students and postdoctoral fellows from both Emory labs.
"It's remarkable to be able to rescue mice from embryonic death," Caspary says. "I was surprised that the mice are even born, since these enzymes are basic parts of the cellular machinery."
In humans, a lack of caspase 8 has been linked to immune disorders and skin diseases such as eczema, while too much caspase 8 activity has been connected with diabetes.
|Contact: Joe Quimby|