The Immunophilin Ligand Rapamycin: A Probe for the Analysis of the Relationship of Apoptosis to the Cell Cycle

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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.



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