Nuclear factor kappaB (NFkappaB) regulates the expression of various genes 
essential for cell survival. Here we demonstrate that suppression of NFkappaB 
nuclear import with SN50 peptide carrying the nuclear localization sequence 
(NLS) of the NFkappaB p50 subunit induces apoptosis in human peripheral blood T 
lymphocytes (T-PBL), which can be blocked with the pan-caspase inhibitor 
Z-VAD.fmk. However, even when caspase function is blocked, the addition of SN50 
induces irreversible cell loss due to the reduction in the mitochondrial 
transmembrane potential (DeltaPsim) followed by disruption of the cell membrane, 
hallmarks of necrosis. These observations demonstrate that although inhibition 
of NFkappaB nuclear translocation by SN50 peptide can induce caspase-dependent 
apoptosis in T-PBL, cell death may still proceed in the absence of functional 
caspase activity. The availability of downstream caspases appears to determine 
the mode of cell death in NFkappaB defective cells.