Armet, a UPR-upregulated protelin, inhibits cell proliferation and ER stress-induced cell death
Armet, a UPR-upregulated protelin, inhibits cell proliferation and ER stress-induced cell death
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DOI：
10.1016/j.yexcr.2008.05.001
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发表时间：
2008-08-01
影响因子：
3.7
通讯作者：
Fang, Shengyun
中科院分区：
文献类型：
--
作者：
Apostolou, Andria;Shen, Yuxian;Fang, Shengyun
内质网 (ER) 中错误折叠蛋白的积累会导致 ER 应激，进而引发未折叠蛋白反应 (UPR)。 UPR 激活适应性和凋亡途径，这两种途径对疾病发病机制的贡献不同。为了进一步了解 UPR 的功能机制，我们通过表达微阵列分析鉴定了 12 个常见的 UPR 上调基因。在这里，我们描述了 Armet/MANF 的特征，这是 12 个功能尚不清楚的基因之一。我们证明了 Armet/MANF 蛋白在多种细胞系中受到各种形式的 ER 应激以及大鼠脑缺血的上调。 Armet/MANF 位于内质网和高尔基体中，也是一种分泌蛋白。在 HeLa 细胞中通过 siRNA 寡核苷酸沉默 Armet/MANF 使细胞更容易受到 ER 应激诱导的死亡的影响，但令人惊讶的是细胞增殖增加并减小了细胞大小。 Armet/MANF 的过度表达在无葡萄糖条件和衣霉素处理下抑制细胞增殖并提高细胞活力。基于我们已经证明的其对增殖和细胞死亡的抑制特性，Armet 是 UPR 适应性途径的一种新型分泌介质。 (c) 2008 Elsevier Inc. 保留所有权利。
The accumulation of misfolded proteins in the endoplasmic reticulum (ER) causes ER stress that initiates the unfolded protein response (UPR). UPR activates both adaptive and apoptotic pathways, which contribute differently to disease pathogenesis. To further understand the functional mechanisms of UPR, we identified 12 commonly UPR-upregulated genes by expression microarray analysis. Here, we describe characterization of Armet/MANF, one of the 12 genes whose function was not clear. We demonstrated that the Armet/MANF protein was upregulated by various forms of ER stress in several cell lines as well as by cerebral ischemia of rat. Armet/MANF was localized in the ER and Golgi and was also a secreted protein. Silencing Armet/MANF by siRNA oligos in HeLa cells rendered cells more susceptible to ER stress-induced death, but surprisingly increased cell proliferation and reduced cell size. Overexpression of Armet/MANF inhibited cell proliferation and improved cell viability under glucose-free conditions and tunicamycin treatment. Based on its inhibitory properties for both proliferation and cell death we have demonstrated, Armet is, thus, a novel secreted mediator of the adaptive pathway of UPR. (c) 2008 Elsevier Inc. All rights reserved.