Reconstitution of Caspase-8 Sensitizes JB6 Cells to TRAIL

TRAIL induces apoptosis in various tumor cells. We report here that caspase-8 is required in TRAIL-induced cell death. Western blot analyses and enzyme assays showed that exposing Jurkat cells to TRAIL resulted in activation of caspases-8 followed by caspase-3 and -9. Acetyl-IETD-fluoromethylketone,...

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Bibliographic Details
Published in:Biochemical and biophysical research communications 2000-10, Vol.277 (2), p.311-316
Main Authors: Kim, In-Ki, Chung, Chul-Woong, Woo, Ha-Na, Hong, Gil-Sun, Nagata, Shinji, Jung, Yong-Keun
Format: Article
Language:English
Subjects:
Apoptosis
Apoptosis Regulatory Proteins
Blotting, Western
Caspase 3
Caspase 8
Caspase 9
Caspases - genetics
Caspases - metabolism
Caspases - physiology
Cysteine Proteinase Inhibitors - pharmacology
Dose-Response Relationship, Drug
Enzyme Activation
Genes, Dominant
Humans
JB6 cells
Jurkat Cells
Membrane Glycoproteins - metabolism
Mutation
Oligopeptides - pharmacology
Peptides - pharmacology
Plasmids - metabolism
Recombinant Fusion Proteins - genetics
Recombinant Fusion Proteins - metabolism
Time Factors
TNF-Related Apoptosis-Inducing Ligand
TRAIL
Tumor Cells, Cultured
Tumor Necrosis Factor-alpha - metabolism
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Summary:TRAIL induces apoptosis in various tumor cells. We report here that caspase-8 is required in TRAIL-induced cell death. Western blot analyses and enzyme assays showed that exposing Jurkat cells to TRAIL resulted in activation of caspases-8 followed by caspase-3 and -9. Acetyl-IETD-fluoromethylketone, a caspase-8 inhibitor, potently suppressed TRAIL-induced cell death compared to acetyl-DEVD-fluoromethylketone and acetyl-LEHD-fluoromethylketone, inhibitors of caspase-3 and caspase-9, respectively. JB6 cells, a caspase-8-deficient Jurkat variant, were completely resistant to TRAIL. However, reconstitution with a caspase-8, but not with caspase-2 or -3, sensitized JB6 cells to subsequent exposure to TRAIL. These results are indicative of the crucial function of caspase-8 in TRAIL-induced apoptosis in Jurkat cells.
ISSN:0006-291X
1090-2104
DOI:10.1006/bbrc.2000.3673