Identification of XAF1 as an antagonist of XIAP anti-caspase activity

The inhibitors of apoptosis (IAPs) suppress apoptosis through the inhibitio n of the caspase cascade and thus are key proteins in the control of cell d eath. Here we have isolated the protein XIAP-associated factor 1 (XAF1) on the basis of its ability to bind XIAP, a member of the IAP family. XIAP sup presses caspase activation and cell death in vitro, and XAF1 antagonizes th ese XIAP activities. Expression of XAF1 triggers a redistribution of XIAP f rom the cytosol to the nucleus. XAF1 is ubiquitously expressed in normal ti ssues, but is present at low or undetectable levels in many different cance r cell lines. Loss of control over apoptotic signalling is now recognized a s a critical event in the development of cancer. Our results indicate that XAF1 may be important in mediating the apoptosis resistance of cancer cells .