Caspase signaling, a conserved inductive cue for metazoan cell differentiation

Caspase signaling pathways were originally discovered as conveyors of programmed cell death, yet a compendium of research over the past two decades have demonstrated that these same conduits have a plethora of physiologic functions. Arguably the most extensive non-death activity that has been attributed to this protease clade is the capacity to induce cell differentiation. Caspase control of differentiation is conserved across diverse metazoan organisms from flies to humans, suggesting an ancient origin for this form of cell fate control. Here we discuss the mechanisms by which caspase enzymes manage differentiation, the targeted substrates that may be common across cell lineages, and the countervailing signals that may be essential for these proteases to ‘execute’ this non-death cell fate.