Activation signal of nuclear factor-κB in response to endoplasmic reticulum stress is transduced via IRE1 and tumor necrosis factor receptor-associated factor 2
Activation signal of nuclear factor-κB in response to endoplasmic reticulum stress is transduced via IRE1 and tumor necrosis factor receptor-associated factor 2
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DOI：
10.1248/bpb.26.931
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发表时间：
2003-07-01
影响因子：
2
通讯作者：
Nomura, Y
中科院分区：
文献类型：
--
作者：
Kaneko, M;Niinuma, Y;Nomura, Y
扰乱内质网（ER）功能的条件导致蛋白质的积累和随后的几种反应的诱导，例如参与蛋白质折叠和c-jun N-末端激酶（JNK）活化的ER驻留分子伴侣的表达增加。这些反应由跨膜激酶/核糖核酸酶IRE 1介导，IRE 1将信号从ER腔转导至胞质溶胶。虽然核转录因子-κ B（NF-κ B）也被ER应激激活，但这种反应是否依赖于IRE 1尚不清楚。在这项研究中，我们发现IRE 1参与了ER应激诱导的NF-κ B活化。NF-κ B被ER应激诱导剂毒胡萝卜素和衣霉素激活。激活被抑制的显性负IRE 1。此外，显性负性TRAF 2也抑制了ER应激对NF-κ B的激活。这些结果表明，ER应激诱导的NF-κ B活化也是由IRE 1-TRAF 2途径介导的，以及JNK活化。
Conditions that perturb the function of the endoplasmic reticulum (ER) lead to an accumulation of proteins and subsequent induction of several responses, such as an increased expression of ER-resident chaperones involved in protein folding and activation of c-jun N-terminal kinase (JNK). These responses are mediated by a transmembrane kinase/ribonuclease, IRE1, which transduces the signal from the ER lumen to the cytosol. Although nuclear transcription factor-kappaB (NF-kappaB) is also activated by ER stress, whether this response depends on IRE1 is unknown. In this study, we show that IRE1 is involved in the activation of NF-kappaB induced by ER stress. NF-kappaB was activated by ER stress-inducing agents, thapsigargin and tunicamycin. The activation was inhibited by a dominant-negative IRE1. In addition, a dominant-negative TRAF2 also suppressed the activation of NF-kappaB by ER stress. These results suggest that ER stress-induced NF-kappaB activation is also mediated by the IRE1-TRAF2 pathway, as well as JNK activation.