Variations in cyclin D1 levels through the cell cycle determine the proliferative fate of a cell

We present evidence that variations in cyclin D1 levels through the cell cycle are essential for continuing proliferation. Cyclin D1 levels must be high during G1 phase for a cell to initiate DNA synthesis, but then must be suppressed to low levels during S phase to allow for efficient DNA synthesis. This suppression during S phase is apparently regulated by cell cycle position alone and occurs automatically during each cell cycle. If the cell is to continue proliferating, cyclin D1 levels must be induced once again during G2 phase. This induction depends upon the activity of proliferative signaling molecules, and ensures that the extracellular environment continues to be conducive for growth. We propose that the suppression of cyclin D1 levels during each S phase ensures that the subsequent induction during G2 phase, and the resulting commitment to continuing proliferation, is closely linked to the cellular growth environment.