Death receptors couple to both cell proliferation and apoptosis

No one will dispute that death receptors do exactly what their name suggests, induce programmed cell death. In addition, however, several reports have recently suggested that these receptors, or their downstream regulators, may also function in certain aspects of cell growth or differentiation. These claims might be met with justifiable skepticism. Certainly there is nothing more opposite in cell fate than growth and death. Yet the signal pathways used by these two processes appear to commingle, and the eventual outcome of the signaling vector may be bent toward one result over the other by seemingly subtle balances among these components. Here, following a brief review of the traditional signal pathways that lead from death receptor activation to apoptosis, I scrutinize the various reports of increased growth or differentiation mediated by these same receptors. I then consider newly identified signal pathways linked to death receptors that might promote growth and, finally, speculate on whether these events represent merely interesting in vitro manipulations or actual physiologically important processes.