Sequestration of TRAF2 into stress granules interrupts tumor necrosis factor signaling under stress conditions
Sequestration of TRAF2 into stress granules interrupts tumor necrosis factor signaling under stress conditions
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DOI：
10.1128/mcb.25.6.2450-2462.2005
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发表时间：
2005-03-01
影响因子：
5.3
通讯作者：
Jang, SK
中科院分区：
文献类型：
--
作者：
Kim, WJ;Back, SH;Jang, SK
细胞应激反应(SR)是一种系统发育保守的保护机制，包括通过将eIF4G等翻译因子募集到不溶性应激颗粒(SGS)中来抑制蛋白质合成，以及通过阻断从肿瘤坏死因子-α(TNF-α)到核因子-kappaB(NF-kappaB)激活的信号通路来阻断促炎反应。然而，这两种生理现象之间的联系还没有被清楚地阐明。我们报道eIF4GI是一种与多种翻译因子相互作用的支架蛋白，它与TRAF2相互作用，TRAF2是一种信号分子，在通过肿瘤坏死因子-α激活核因子-kappaB的过程中发挥关键作用。在细胞暴露于应激条件下，这两种蛋白共存于SGS中。此外，在应激条件下，即使在肿瘤坏死因子-α处理后，TNFR1复合体中也不存在TRAF2。这表明，应激细胞通过蛋白质-蛋白质相互作用将翻译因子和TRAF2隔离成SGS，从而降低了它们的生物学活性。
The cellular stress response (SR) is a phylogenetically conserved protection mechanism that involves inhibition of protein synthesis through recruitment of translation factors such as eIF4G into insoluble stress granules (SGs) and blockade of proinflammatory responses by interruption of the signaling pathway from tumor necrosis factor alpha (TNF-alpha) to nuclear factor-kappaB (NF-kappaB) activation. However, the link between these two physiological phenomena has not been clearly elucidated. Here we report that eIF4GI, which is a scaffold protein interacting with many translation factors, interacts with TRAF2, a signaling molecule that plays a key role in activation of NF-kappaB through TNF-alpha. These two proteins colocalize in SGs during cellular exposure to stress conditions. Moreover, TRAF2 is absent from TNFR1 complexes under stress conditions even after TNF-alpha treatment. This suggests that stressed cells lower their biological activities by sequestration of translation factors and TRAF2 into SGs through a protein-protein interaction.