Two caspases work together to determine a cell's propensity for apoptosis, Florentin and Arama show.

Whether an injured cell commits suicide depends on factors such as what tissue it inhabits. A cell's tendency to undergo apoptosis can even change during its lifetime. These differences have intrigued cancer and developmental biologists for years, but researchers have yet to agree on an explanation for cells’ variable sensitivities. Florentin and Arama investigated two effector caspases that spur Drosophila cells to commit suicide. The two killer proteins, Drice and Dcp-1, are the equivalents of caspase-3 and caspase-7 in mammals.

Although Drice and Dcp-1 cleave similar proteins, they play different roles during apoptosis, the researchers concluded after studying cell death in the larval imaginal disc that becomes the adult fly's wing. Control cells and cells lacking Dcp-1 killed themselves after a dose of radiation. However, cells that were missing Drice remained alive. That doesn't mean Dcp-1 is a pacifist. It is able to trigger apoptosis, Florentin and Arama confirmed when they inserted extra copies of the Dcp-1 gene into cells lacking Drice.

However, Drice appears to be the better of the two caspases at inducing cells to kill themselves. Dcp-1, meanwhile, helps control the rate at which cells die, partly by switching on more Drice. The researchers hypothesize that, by adjusting the ratio of the two caspases, cells can set their sensitivity to apoptosis-inducing stimuli.

J. Cell Biol.