elopment. The gene ced-4 encodes a novel protein, but ced-3 is a homolog of ICE (interleukin-1b converting enzyme). Experiments demonstrate the link between the gene ICE and apoptosis. Rat fibroblasts genetically engineered to overproduce ICE die by apoptosis, and phagocytes gain ICE after gobbling apoptotic cells. Recently, Junying Yuan--an associate professor in the department of medicine at Harvard Medical School--and her colleagues, working with a chicken neuron cell culture, found that inhibiting ICE activity prevents the cells from dying when their supply of nerve growth factor is blocked (V. Gagliardini et al., Science, 263:826-8, 1994). Another "apoptosis on" gene receiving much attention is p53. The gene, which encodes a transcription factor and is common in many human cancers, mediates cellular responses to some environmental damage. The p53 protein either temporarily halts cell division so the cell can repair altered DNA, or sends the cell to an apoptotic death. "How p53 makes that choice is the $64,000 question. Maybe there is a threshold. If damage is minor, the cell takes the time to repair it. But if damage is above threshold, it bails out, choosing apoptosis. The threshold may be different in different cell types," says Alexander Kamb, director of research at Myriad Genetics Inc. in Salt Lake City, Utah. Adds Steven Schreiber, an assistant professor of neurology at the University of Southern California School of Medicine: "Maybe the choice of cell death or arrest of the cell cycle depends on the proliferative capacity of the cell--if it has a certain number of cycles to go. Or, it may depend upon the stage of the cell cycle when the damage occurs." Work on p53 reveals that there are different means to an apoptotic end. "Our work with Tyler Jacks [a professor of biology] at MIT shows that p53 only kills thymocytes when the inducer to death is radiation," says Osborne. Other thymic inducers include glucocorticoids and cros...
