Programmed cell death: a missing link is found

Two families of proteins have advanced our understanding of the molecular basis of programmed cell death (PCD) in animal cells - the caspases and Bcl-2-related proteins. While caspases lie at the heart of the death programme, Bcl-2-related proteins act as key intracellular regulators. Although there has been considerable progress in elucidating the biochemical functions of caspases, how Bcl-2-related proteins regulate caspase activation and thereby PCD, has remained a mystery. One key to resolving this mystery seems to lie with a new third family of proteins related to the Caenorhabditis elegans cell-death protein CED-4, which connects Bcl-2-related proteins to caspases. An important step in defining this new family has been made by the identification of a human CED-4 homologue.