The immunophilin ligand rapamycin: A probe for the analysis of the relationship of apoptosis to the cell cycle

A common consequence of growth factor deprivation in actively proliferating cells is arrest in the G₁ phase of the cell cycle and subsequent apoptosis (programmed cell death). We have utilized the potent cell cycle inhibitor rapamycin (Rapa) to define move precisely the point within G₁ where apoptosis is initiated during IL-2 deprivation in murine CTLL cells. Our results indicate that apoptosis is not initiated at a single point within G₁, but rather can be initiated in at least two distinct points of the cell cycle, early and late G₁. In nonproliferating CTLL cells arrested with Rapa in late G₁, IL-2 prevents the initiation of an apoptotic response. This suggests that an IL-2-mediated signal is necessary to prevent apoptosis when proliferation is blocked, whether the block to proliferation arrests cells in early or late G₁.