Figure 7. A hypothesis for Keap1-mediated hepatic redox cycle and hepatocyte cell cycle in regenerating livers. Redox sensor Keap1 modulates the cycle of free radicals produced by regenerating livers by both Nrf2-depedent and -independent mechanisms. Keap1 also regulates the activities of hepatocyte mitogenic signaling molecules, including c-Met, EGFR, Akt1, and p70S6K, and their downstream effectors, including Cyclins A2 and B1. Nrf2 needs to be kept quiescent when hepatocytes are replicating. The threshold of Keap1 expression is tightly controlled to ensure the proper coupling of hepatic redox cycle and hepatocyte cell cycle, thereby enabling hepatocytes to enter and progress through the cell cycle smoothly and rhythmically during liver regeneration.