DEDD spells death to caspase substrates

The major apoptotic effector protein caspase-3 holds the power to destroy a huge number of proteins in a cell—over 34 thousand human proteins with a caspase-3 cleavage motif have been sequenced. Nevertheless, apoptosis proceeds in an ordered fashion; only specific substrates are cleaved at the proper time. On page 1051, Lee et al. describe a new function of the apoptosis regulator DEDD as a scaffolding protein that directs this orderly destruction.

DEDD works by bringing together the important participants, much like scaffolding proteins that control signaling cascades. DEDD resides mainly in the cytosol, despite its previous identification based on its DNA-binding death effector domain (DED). Localization studies by Lee et al. revealed that, even in nonapoptotic epithelial cells, DEDD associated with the keratin intermediate filament network. Once apoptosis was induced, an apoptosis-related epitope within the...