SEKI-dependent JNK1 activation prolongs cell survival during G-Rh2-induced apoptosis
SEKI-dependent JNK1 activation prolongs cell survival during G-Rh2-induced apoptosis
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DOI：
10.1016/s0006-291x(03)00591-6
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发表时间：
2003-05-02
影响因子：
3.1
通讯作者：
Lee, SK
中科院分区：
文献类型：
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作者：
Ham, YM;Chun, KH;Lee, SK
我们在此提供的证据表明，在用人参皂苷 Rh2 (G-Rh2) 处理后 SK-HEP-1 细胞凋亡过程中，c-Jun N 末端蛋白激酶 I (JNK1) 活性差异上调。前 10-30 分钟发生的 G-Rh2 介导的 JNK1 激活与 SEK1 活性相关，但此后，持续激活与 SEK1 活性无关，而是与 JNK1 相关 p21 (WAF1/CIP1) 的蛋白水解裂解相关。支持这一点的是显性失活 SEK1 突变体的表达有效地阻断了早期 JNK1 激活阶段，但没有改变持续激活阶段或细胞凋亡。此外，p21D112N 的表达。 p21（WAF1/CIP1）的不可切割突变体抑制了后来的 JNK1 激活。此外，异位JNK1的稳定过表达抑制了细胞凋亡，而显性失活JNK1突变体的表达则促进了细胞凋亡。我们提出，早期 SEK1 相关的 JNK1 激活阶段可延长细胞对凋亡诱导剂的存活时间，从而作为细胞凋亡之前的干预检查点。 (C) 2003 年爱思唯尔科学（美国）。版权所有。
We provide here evidence that c-Jun N-terminal protein kinase I (JNK1) activity is differentially up-regulated during apoptosis of SK-HEP-1 cells after treatment with ginsenoside Rh2 (G-Rh2). The G-Rh2-mediated JNK1 activation that occurred for the first 10-30 min was associated with SEK1 activity, but thereafter, the sustained activation was associated not with SEK1 activity, but with proteolytic cleavage of JNK1-associated p21(WAF1/CIP1). Supporting this is that the expression of the dominant negative SEK1 mutant effectively blocked the early JNK1 activation phase but did not alter the sustained activation phase or apoptosis. Furthermore, expression of p21D112N. an uncleavable mutant of p21(WAF1/CIP1) suppressed the later JNK1 activation. Moreover, the stable overexpression of ectopic JNK1 suppressed apoptosis while expression of the dominant negative JNK1 mutant promoted it. We propose that the early SEK1-associated JNK1 activation phase acts to prolong cell survival in response to apoptosis-inducing agents, thereby serving as an intervening checkpoint prior to the commitment to apoptosis. (C) 2003 Elsevier Science (USA). All rights reserved.