When Seamus J. Martin, professor of medical genetics at the Smurfit Institute, Trinity College in Dublin, Ireland, and colleagues began their work, they knew of an apoptosis pathway involving caspase-3 activation.1 It was triggered by release of cytochrome c from the mitochondrion into the cytoplasm, where it bound to a caspase-activating protein, Apaf-1. But "it was not clear which of the 12 human caspases were recruited by Apaf-1," Martin recalls. There was an exciting suspicion that they formed a cascade triggered by Apaf-1/cytochrome c, similar in kind to the proteolytic complement activation cascade. Their aim, he says, was "to identify how many caspases were involved in the cascade and unravel the order of events."
Martin collaborated with postdoc Elizabeth Slee, now at the Ludwig Cancer Research Institute in London, and Doug Green, of the La Jolla Institute for Allergy and Immunology in San Diego. Their experiments used a cell-free model ...
