Abstract
Expression of BAX, without another death stimulus, proved sufficient to induce a common pathway of apoptosis. This included the activation of interleukin 1β-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.
Keywords
ProteasesProgrammed cell deathProteaseApoptosisCytosolPoly ADP ribose polymeraseEnzymeBiologyBiochemistryCell biologyCaspaseMitochondrionChemistryMolecular biologyPolymerase
MeSH Terms
ApoptosisCaspase 1Cysteine EndopeptidasesHumansJurkat CellsMitochondriaProto-Oncogene ProteinsProto-Oncogene Proteins c-bcl-2Reactive Oxygen SpeciesSignal Transductionbcl-2-Associated X Protein
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Publication Info
- Year
- 1996
- Type
- article
- Volume
- 93
- Issue
- 25
- Pages
- 14559-14563
- Citations
- 899
- Access
- Closed
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Cite This
Jialing Xiang,
Debra T. Chao,
Stanley J. Korsmeyer
(1996).
BAX-induced cell death may not require interleukin 1β-converting enzyme-like proteases.
Proceedings of the National Academy of Sciences
, 93
(25)
, 14559-14563.
https://doi.org/10.1073/pnas.93.25.14559
Identifiers
- DOI
- 10.1073/pnas.93.25.14559
- PMID
- 8962091
- PMCID
- PMC26172