Disassembly of the JIP1/JNK molecular scaffold by caspase-3-mediated cleavage of JIP1 during apoptosis.
Disassembly of the JIP1/JNK molecular scaffold by caspase-3-mediated cleavage of JIP1 during apoptosis.
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DOI：
10.1016/j.yexcr.2011.01.011
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发表时间：
2011-04-15
影响因子：
3.7
通讯作者：
Dickens M
中科院分区：
文献类型：
--
作者：
Vaishnav M;MacFarlane M;Dickens M
我们在此报道了在肿瘤坏死因子相关凋亡诱导配体（TRAIL）和staurosporine诱导的HeLa细胞凋亡过程中，半胱天酶对c-Jun n-末端激酶（JNK）通路支架蛋白，JNK相互作用蛋白-1 （JIP1）的切割。在细胞凋亡开始过程中，当JIP1完整时，JNK激活最大，而JIP1的切割与JNK失活和细胞凋亡的进展相关。JIP1在两个位点被caspase-3切割，导致JIP1/JNK复合体解体。caspase-3抑制剂DEVD对JIP1裂解的抑制作用。fmk抑制这种分解，并伴随着持续的JNK激活。这些数据表明，TRAIL和staurosporine以不依赖于caspase-3的方式诱导JNK活化，并且caspase-3介导的JIP1裂解在细胞凋亡执行阶段通过支架的解体参与JNK失活。因此，caspase介导的JIP支架蛋白的裂解可能是凋亡细胞死亡过程中JNK信号调节的重要机制。
We report here the cleavage of the c-Jun N-terminal Kinase (JNK) pathway scaffold protein, JNK Interacting Protein-1 (JIP1), by caspases during both Tumour Necrosis Factor-Related Apoptosis-Inducing Ligand (TRAIL) and staurosporine-induced apoptosis in HeLa cells. During the initiation of apoptosis, maximal JNK activation is observed when JIP1 is intact, whereas cleavage of JIP1 correlates with JNK inactivation and progression of apoptosis. JIP1 is cleaved by caspase-3 at two sites, leading to disassembly of the JIP1/JNK complex. Inhibition of JIP1 cleavage by the caspase-3 inhibitor DEVD.fmk inhibits this disassembly, and is accompanied by sustained JNK activation. These data suggest that TRAIL and staurosporine induce JNK activation in a caspase-3-independent manner and that caspase-3-mediated JIP1 cleavage plays a role in JNK inactivation via scaffold disassembly during the execution phase of apoptosis. Caspase-mediated cleavage of JIP scaffold proteins may therefore represent an important mechanism for modulation of JNK signalling during apoptotic cell death.
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