DEATH-EFFECTOR FILAMENTS - NOVEL CYTOPLASMIC STRUCTURES THAT RECRUIT CASPASES AND TRIGGER APOPTOSIS

The death-effector domain (DED) is a critical protein interaction doma in that recruits caspases into complexes with members of the TNF-recep tor superfamily. Apoptosis can also be induced by expressing certain D ED-containing proteins without surface receptor cross-linking. Using G reen Fluorescent Protein to examine DED-containing proteins in living cells, we show that these proteins cause apoptosis by forming novel cy toplasmic filaments that recruit and activate pro-caspase zymogens. Fo rmation of these filaments, which we term death-effector filaments, wa s blocked by coexpression of viral antiapoptotic DED-containing protei ns, but not by bcl-2 family proteins. Thus, formation of death-effecto r filaments allows a regulated intracellular assembly of apoptosis-sig naling complexes that can initiate or amplify apoptotic stimuli indepe ndently of receptors at the plasma membrane.