TY - JOUR
T1 - Caspase-mediated cleavage of JNK during stress-induced apoptosis
AU - Enomoto, Atsushi
AU - Suzuki, Norio
AU - Morita, Akinori
AU - Ito, Michihiko
AU - Liu, Chang Qing
AU - Matsumoto, Yoshihisa
AU - Yoshioka, Katsuji
AU - Shiba, Tadayoshi
AU - Hosoi, Yoshio
N1 - Funding Information:
This work was supported partly by grants from the Ministry of Education, Culture, Sport, Science and Technology, and the Ministry of Health and Welfare of Japan.
PY - 2003/7/11
Y1 - 2003/7/11
N2 - 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.
AB - 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.
KW - Caspase
KW - Cleavage site
KW - JNK
KW - X-irradiation
KW - p52
KW - p54
UR - http://www.scopus.com/inward/record.url?scp=0037757743&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0037757743&partnerID=8YFLogxK
U2 - 10.1016/S0006-291X(03)01050-7
DO - 10.1016/S0006-291X(03)01050-7
M3 - Article
C2 - 12821118
AN - SCOPUS:0037757743
SN - 0006-291X
VL - 306
SP - 837
EP - 842
JO - Biochemical and Biophysical Research Communications
JF - Biochemical and Biophysical Research Communications
IS - 4
ER -