Two well-defined protein-protein interaction domains have been found in ini tiator caspases. C. elegans CED-3, Drosophila DRONC, and mammalian caspases1, -2, -4, -5, -9, -11, and -12 contain a caspase recruitment domain (CARD) in their prodomain, whereas Drosophila DREDD and mammalian caspases -8 and -10 con-
tain a pair of death effector domains (DEDs) in their prodomain regions (reviewed in Kumar, 1999; Kumar and Colussi, 1999; Shi, 2002) (Figure 1). A number of other caspases, including C. elegans CSP-1 and CSP-2, and Drosophila STRICA, have long prodomains, lacking any CARD or DED (Shaham, 1998; Doumanis et al., 2001). While the CARDs and DEDs in some caspases clearly play a role in caspase activation, the function of long prodomains in CSP-1, CSP-2, and STRICA is currently unclear.