The general mechanistic interplay of the C. elegans cell death
machinery is conserved, albeit with substantial embellishments, in
other metazoans. Multiple caspases are present in both Drosophila and
mammals, and these are in turn regulated by various homologues and
analogues of the CED-4 adaptor/scaffold protein of which the evolutionarily
closest known functional relatives are Apaf-1 in man14 and
dApaf-1/DARK/HAC-1 in flies15–17. In addition, in mammals at least,
certain caspases are activated by recruitment into complexes induced
by ligation of death receptors such as CD95 (Apo-1/Fas) and tumour
necrosis factor (TNF) receptor 1 (see review in this issue by Krammer,
pages 789–795). The mammalian18 and recently identified Drosophila19–
22counterparts of the CED-9 death suppressor protein are the Bcl-2
family of proteins which, in mammals (and maybe in Drosophila),
includes both anti-apoptotic (‘CED-9/Bcl-2-like’) and BH3 proapoptotic
(‘EGL-1-like’) members23. The remarkable conservation of
molecular mechanism by which Bcl-2 proteins prevent cell death is
most graphically demonstrated by the fact that human Bcl-2 is fully
functional in suppressing cell deaths in developing C. elegans24.