XAF1 is a zinc finger protein that binds to XIAP and neutralizes its function. XIAP is a member of the inhibitor of apoptosis (IAP) family, which inhibits apoptosis by directly inhibiting caspases, the enzymes responsible for the execution of apoptosis . By binding to XIAP, XAF1 promotes the activation of caspases, thereby facilitating apoptosis.
XAF1 functions as a tumor suppressor. It has been shown to cooperate with tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) to suppress the growth of colon cancer and trigger tumor regression . The combined restoration of XAF1 expression and TRAIL treatment has been found to significantly enhance apoptosis and inhibit tumor growth in colon cancer models .
The mechanism by which XAF1 antagonizes XIAP involves the release of cytochrome c from mitochondria, which then activates caspases 3, 7, 8, and 9 . This leads to the down-regulation of XIAP, survivin, and c-IAP-2, which are proteins that inhibit apoptosis . The restoration of XAF1 expression directly induces apoptosis and enhances the apoptotic effects of TRAIL .
Given its role in promoting apoptosis and suppressing tumor growth, XAF1 is being investigated as a potential therapeutic target for cancer treatment. Strategies that involve the restoration of XAF1 expression or the use of recombinant XAF1 protein in combination with other apoptotic agents like TRAIL are being explored for their potential to treat various cancers .