Analysis of double-stranded RNA-induced apoptosis pathways using interferon-response noninducible small interfering RNA expression vector library
Analysis of double-stranded RNA-induced apoptosis pathways using interferon-response noninducible small interfering RNA expression vector library
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DOI：
10.1074/jbc.m412784200
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发表时间：
2005-07-08
影响因子：
4.8
通讯作者：
Taira, K
中科院分区：
文献类型：
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作者：
Matsumoto, S;Miyagishi, M;Taira, K
我们已经开发了一个原始的载体库，使我们能够利用RNA干扰现象，但也使我们能够避免干扰素反应的混淆效应。在目前的工作中，我们使用我们的小干扰RNA表达载体库来检查参与由双链RNA诱导的细胞凋亡的基因。令人惊讶的是，我们的文库筛选发现两个新的双链RNA诱导的凋亡途径，JNK/SAPK介导的线粒体途径和ERK 2相关的途径，这两个似乎是独立的丝氨酸-苏氨酸蛋白激酶依赖的caspase途径。我们还发现MST 2和蛋白激酶C α都激活了ERK 2介导的促凋亡信号。我们的筛选分析的结果表明，小干扰RNA表达载体的文库的大规模筛选的效用。
We have developed an original vector library that allowed us to exploit the phenomenon of RNA interference but also allowed us to avoid the confounding effects of the interferon response. In the present work, we used our library of small interfering RNA expression vectors to examine the genes involved in apoptosis that was induced by double-stranded RNA. To our surprise, screening of our library revealed two novel double-stranded RNA-induced apoptotic pathways, a JNK/SAPK-mediated mitochondrial pathway and an ERK2-related pathway, both of which appeared to be independent of the serine-threonine protein kinase-dependent caspase pathway. We also found that MST2 and protein kinase C alpha both activated the proapoptotic signal mediated by ERK2. The results of our screening analysis suggested the utility of large scale screenings with libraries of small interfering RNA expression vectors.