Figure 1.

FHIT: suppressor and caretaker. In response to oxidative stress, FHIT protein localizes to the mitochondria via Hsp complex where it interacts with and stabilizes ferredoxin reductase, leading to enhanced production of reactive oxygen species, stimulation of cytochrome c release and subsequent activation of the Caspase cascade under conditions of severe oxidative stress. In response to genotoxic stress, FHIT participates in the checkpoint response to DNA damage via Chk1 to commit cells to cell cycle arrest and, if DNA damage is extensive, to apoptosis. Importantly, FHIT-deficient cells are resistant to oxidative and genotoxic agents and develop preneoplastic changes.