A massive machine regulates cell death

Abstract

Cells are bombarded with signals about their environment, which they integrate to decide an appropriate response. Danger signals elicit the most drastic of these decisions-is the situation salvageable, or should the cell be sacrificed? When danger signals predominate, one of several pathways induces cell death, with apoptosis being the most common. The key executioners of apoptosis are proteases called caspases; when caspases are activated, apoptosis becomes irreversible. Caspase activation is tightly controlled by regulatory molecules, including the inhibitor of apoptosis (IAP) proteins. The largest and most diverse member of the IAP family, baculoviral IAP repeat-containing protein 6 (BIRC6), has remained an enigma. On pages 1105, 1112, and 1117 of this issue, Hunkeler et al. (1), Dietz et al. (2), and Ehrmann et al. (3), respectively, reveal the molecular basis of how BIRC6 controls cell fate, which may ultimately inform the development of new anticancer drugs that induce cell death.