A redox cycle within the cell cycle: ring in the old with the new

In recent years, the intracellular oxidation-reduction ( redox) state has gained increasing attention as a critical mediator of cell signaling, gene expression changes and proliferation. This review discusses the evidence for a redox cycle ( i. e., fluctuation in the cellular redox state) regulating the cell cycle. The presence of redox-sensitive motifs ( cysteine residues, metal co-factors in kinases and phosphatases) in several cell cycle regulatory proteins indicate periodic oscillations in intracellular redox state could play a central role in regulating progression from G(0)/G(1) to S to G(2) and M cell cycle phases. Fluctuations in the intracellular redox state during cell cycle progression could represent a fundamental mechanism linking oxidative metabolic processes to cell cycle regulatory processes. Proliferative disorders are central to a variety of human pathophysiological conditions thought to involve oxidative stress. Therefore, a more complete understanding of redox control of the cell cycle could provide a biochemical rationale for manipulating aberrant cell proliferation.