addition to the regions that give rise to two subunits, procaspases contain N—
terminal prodomains of varying lengths. By the length of prodomain, caspases can
be divided into two groups: those containing a relatively long prodomain, and those
containing a short prodomain (Figure 1). The long prodomains in many caspases
consist of specific protein-protein interaction domains that play a crucial role in
caspase activation (reviewed in Kumar, 1999; Kumar and Colussi, 1999; Shi, 2002).
These prodomains seem to mediate recruitment of the procaspase molecules to
specific death complexes. This recruitment of procaspase molecules, mediated by
specific adaptor molecules, results in caspase activation by autocatalysis. Thus, the
caspases that get activated via recruitment to specific signaling complexes are also
known as the initiator caspases. The main initiator caspases are caspases-8, -9, and
-10 in mammals and DRONC in Drosophila (reviewed in Nicholson, 1999; Kumar
and Doumanis, 2000). Caspases that lack a long amino-terminal prodomain also lack
the ability to self-activate and require cleavage by activated initiator caspases. As most
of the cellular caspase substrates are cleaved by these downstream caspases, these
caspases are often referred to as the effector caspases. The key effector caspases in
mammals include caspases-3, -6, and -7, and in Drosophila DCP-1 and DRICE
(reviewed in Nicholson, 1999; Kumar and Doumanis, 2000).
Two well-defined protein-protein interaction domains have been found in initiator
caspases. C.elegans CED-3, Drosophila DRONC, and mammalian caspases-1, -2, -4,
Figure 1. Prodomains define various types of caspases.-5, -9, -11, and -12 contain a caspase recruitment domain (CARD) in their
prodomain, whereas Drosophila DREDD and mammalian caspases -8 and -10
34 GENETICS OF APOPTOSIS