Caspase-mediated cleavage of JNK during stress-induced apoptosis

The c-Jun N-terminal kinases (JNKs) are a subfamily of the mitogen-activated protein kinases (MAPKs). The JNKs are encoded by three separate genes ( jnk1, jnk2, and jnk3), which are spliced alternatively to create 10 JNK isoforms that are either p46 or p54 in size. In this study, we found that the p...

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Bibliographic Details
Published in:Biochemical and biophysical research communications 2003-07, Vol.306 (4), p.837-842
Main Authors: Enomoto, Atsushi, Suzuki, Norio, Morita, Akinori, Ito, Michihiko, Liu, Chang Qing, Matsumoto, Yoshihisa, Yoshioka, Katsuji, Shiba, Tadayoshi, Hosoi, Yoshio
Format: Article
Language:English
Subjects:
Alternative Splicing
Apoptosis
Blotting, Western
Caspase
Caspase 3
Caspases - metabolism
Cell Line
Cleavage site
Enzyme Inhibitors - pharmacology
Gene Deletion
Humans
JNK
Mitogen-Activated Protein Kinase 8
Mitogen-Activated Protein Kinase 9
Mitogen-Activated Protein Kinases - metabolism
Oligopeptides - pharmacology
Open Reading Frames
p52
p54
Phosphorylation
Plasmids - metabolism
Protein Isoforms
Recombinant Proteins - metabolism
Reverse Transcriptase Polymerase Chain Reaction
Time Factors
Tumor Cells, Cultured
U937 Cells
X-irradiation
X-Rays
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Summary:The c-Jun N-terminal kinases (JNKs) are a subfamily of the mitogen-activated protein kinases (MAPKs). The JNKs are encoded by three separate genes ( jnk1, jnk2, and jnk3), which are spliced alternatively to create 10 JNK isoforms that are either p46 or p54 in size. In this study, we found that the p52 form of JNK emerged in human leukemia MOLT-4 or U937 cells following X-irradiation or heat treatment. The accumulation of p52 coincided with the reduction of p54 JNK. On the other hand, the amounts of p46 JNK did not change by X-irradiation. Induction of the p52 form of JNK also paralleled the appearance of the active form of caspase-3 and was suppressed by a caspase-specific inhibitor, Ac-DEVD-CHO, but not by Ac-YVAD-CHO. In vitro cleavage assays indicated that recombinant human JNK1β2 and JNK2β2 were cleaved by caspase-3, and that the mutation of aspartic acid at position 413 of JNK1β2 or 410 of JNK2β2 to alanine abolished the cleavage. Altogether, our results demonstrated that p54 JNKs, at least JNK1β2 and JNK2β2, were new selective targets of caspases in JNK splicing variants, and suggested that the p52 form could serve as a marker of apoptosis.
ISSN:0006-291X
1090-2104
DOI:10.1016/S0006-291X(03)01050-7