The study investigates whether BAX-induced cell death requires the activation of interleukin 1β-converting enzyme (ICE)-like proteases. BAX, a member of the Bcl-2 family, is known to function as a death agonist in apoptosis. The researchers used a reverse tetracycline-inducible system in Jurkat T cells to induce BAX expression and observed that BAX alone was sufficient to trigger apoptosis, characterized by nuclear condensation, DNA fragmentation, membrane blebbing, and cell shrinkage. However, the activation of ICE-like proteases, which are crucial for certain aspects of cell death, was not necessary for BAX-induced apoptosis. Inhibition of these proteases prevented the cleavage of specific substrates like poly(ADP-ribose) polymerase (PARP) and D4-GDI, but it did not block BAX-induced cell death. Instead, other downstream events such as the reduction of mitochondrial membrane potential and the production of reactive oxygen species (ROS) continued to occur. These findings suggest that BAX-induced apoptosis may involve a pathway that is independent of known ICE-like proteases, possibly involving mitochondrial dysfunction.The study investigates whether BAX-induced cell death requires the activation of interleukin 1β-converting enzyme (ICE)-like proteases. BAX, a member of the Bcl-2 family, is known to function as a death agonist in apoptosis. The researchers used a reverse tetracycline-inducible system in Jurkat T cells to induce BAX expression and observed that BAX alone was sufficient to trigger apoptosis, characterized by nuclear condensation, DNA fragmentation, membrane blebbing, and cell shrinkage. However, the activation of ICE-like proteases, which are crucial for certain aspects of cell death, was not necessary for BAX-induced apoptosis. Inhibition of these proteases prevented the cleavage of specific substrates like poly(ADP-ribose) polymerase (PARP) and D4-GDI, but it did not block BAX-induced cell death. Instead, other downstream events such as the reduction of mitochondrial membrane potential and the production of reactive oxygen species (ROS) continued to occur. These findings suggest that BAX-induced apoptosis may involve a pathway that is independent of known ICE-like proteases, possibly involving mitochondrial dysfunction.