Inhibition of protein translocation at the endoplasmic reticulum promotes activation of the unfolded protein response.
Inhibition of protein translocation at the endoplasmic reticulum promotes activation of the unfolded protein response.
复制标题
抑制内质网的蛋白质易位会促进展开的蛋白质反应的激活。
DOI：
10.1042/bj20111220
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发表时间：
2012-03-15
期刊：
影响因子：
--
通讯作者：
Swanton E
中科院分区：
文献类型：
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作者：
McKibbin C;Mares A;Piacenti M;Williams H;Roboti P;Puumalainen M;Callan AC;Lesiak-Mieczkowska K;Linder S;Harant H;High S;Flitsch SL;Whitehead RC;Swanton E
选择性小分子抑制剂是研究复杂生物过程的有力工具。ESI（eeyarestatin I）是一种新型的内质网（endoplasmic reticulum）功能调节剂。在本研究中，我们表明，除了急性抑制ERAD（ER相关的降解），ESI引起的错误定位的多肽，是泛素化和降解的生产。出乎意料的是，我们的结果表明，这些非易位的多肽促进激活的UPR（未折叠的蛋白质反应），事实上，我们可以概括UPR激活与替代和相当不同的抑制剂ER易位。这些结果表明，非易位蛋白质在胞质溶胶中的积累可能代表了一种新的机制，有助于UPR激活。
Selective small-molecule inhibitors represent powerful tools for the dissection of complex biological processes. ESI (eeyarestatin I) is a novel modulator of ER (endoplasmic reticulum) function. In the present study, we show that in addition to acutely inhibiting ERAD (ER-associated degradation), ESI causes production of mislocalized polypeptides that are ubiquitinated and degraded. Unexpectedly, our results suggest that these non-translocated polypeptides promote activation of the UPR (unfolded protein response), and indeed we can recapitulate UPR activation with an alternative and quite distinct inhibitor of ER translocation. These results suggest that the accumulation of non-translocated proteins in the cytosol may represent a novel mechanism that contributes to UPR activation.