title: BAX-induced cell death may not require interleukin 1 beta-converting enzyme-like proteases.
abstract: Expression of BAX, without another death stimulus, proved sufficient to induce a common pathway of apoptosis. This included the activation of interleukin 1 beta-converting enzyme (ICE)-like proteases with cleavage of the endogenous substrates poly(ADP ribose) polymerase and D4-GDI (GDP dissociation inhibitor for the rho family), as well as the fluorogenic peptide acetyl-Asp-Glu-Val-Asp-aminotrifluoromethylcoumarin (DEVD-AFC). The inhibitor benzyloxycarbonyl-Val-Ala-Asp-fluoromethyl ketone (zVAD-fmk) successfully blocked this protease activity and prevented FAS-induced death but not BAX-induced death. Blocking ICE-like protease activity prevented the cleavage of nuclear and cytosolic substrates and the DNA degradation that followed BAX induction. However, the fall in mitochondrial membrane potential, production of reactive oxygen species, cytoplasmic vacuolation, and plasma membrane permeability that are downstream of BAX still occurred. Thus, BAX-induced alterations in mitochondrial function and subsequent cell death do not apparently require the known ICE-like proteases.
authors.affiliation: Department of Medicine and Pathology, Howard Hughes Medical Institute, Washington University, St. Louis, MO 63110, USA.
authors.forename: J
authors.initials: J
authors.lastname: Xiang
authors.forename: D T
authors.initials: DT
authors.lastname: Chao
authors.forename: S J
authors.initials: SJ
authors.lastname: Korsmeyer
mesh_terms: D017209:Apoptosis / Q000502:physiology*; D020170:Caspase 1; D003546:Cysteine Endopeptidases / Q000502:physiology*; D006801:Humans; D019169:Jurkat Cells; D008928:Mitochondria / Q000502:physiology*; D011518:Proto-Oncogene Proteins / Q000502:physiology*; D019253:Proto-Oncogene Proteins c-bcl-2; D017382:Reactive Oxygen Species; D015398:Signal Transduction; D051028:bcl-2-Associated X Protein
chemical_list: C494826:BAX protein, human; D011518:Proto-Oncogene Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; D017382:Reactive Oxygen Species; D051028:bcl-2-Associated X Protein; D003546:Cysteine Endopeptidases; D020170:Caspase 1