Caspase-mediated cleavage of JNK during stress-induced apoptosis
Caspase-mediated cleavage of JNK during stress-induced apoptosis
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DOI：
10.1016/s0006-291x(03)01050-7
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发表时间：
2003-07-11
影响因子：
3.1
通讯作者：
Hosoi, Y
中科院分区：
文献类型：
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作者：
Enomoto, A;Suzuki, N;Hosoi, Y
c-Jun N-末端激酶（JNK）是丝裂原活化蛋白激酶（MAPK）的一个亚家族。JNK由三个独立的基因（jnk 1，jnk-2和jnk 3）编码，它们被交替剪接以产生10种大小为p46或p54的JNK亚型。在本研究中，我们发现JNK的p52形式出现在人白血病MOLT-4或U937细胞后，X射线照射或热处理。p52的积累与p54 JNK的减少一致。另一方面，p46 JNK的量不受X射线照射的影响。p52形式的JNK的诱导也抑制了半胱天冬酶-3活性形式的出现，并且被半胱天冬酶特异性抑制剂Ac-DEVD-CHO抑制，但不被Ac-YVAD-CHO抑制。体外切割试验表明，重组人JNK 1 β 2和JNK 2 β 2被半胱天冬酶-3切割，并且JNK 1 β 2的413位或JNK 2 β 2的410位天冬氨酸突变为丙氨酸消除了切割。总之，我们的研究结果表明，p54 JNK，至少JNK 1 β 2和JNK 2 β 2，是新的选择性靶点的半胱天冬酶在JNK剪接变异体，并建议p52形式可以作为一个标志物的凋亡。(C)2003 Elsevier Science（美国）。All rights reserved.
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, jnk-2, 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 JNK1beta2 and JNK2beta2 were cleaved by caspase-3, and that the mutation of aspartic acid at position 413 of JNK1beta2 or 410 of JNK2beta2 to alanine abolished the cleavage. Altogether, our results demonstrated that p54 JNKs, at least JNK1beta2 and JNK2beta2, were new selective targets of caspases in JNK splicing variants, and suggested that the p52 form could serve as a marker of apoptosis. (C) 2003 Elsevier Science (USA). All rights reserved.