Herp, a new ubiquitin-like membrane protein induced by endoplasmic reticulum stress
Herp, a new ubiquitin-like membrane protein induced by endoplasmic reticulum stress
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DOI：
10.1074/jbc.m002063200
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发表时间：
2000-10-20
影响因子：
4.8
通讯作者：
Miyata, T
中科院分区：
文献类型：
--
作者：
Kokame, K;Agarwala, KL;Miyata, T
高同型半胱氨酸血症是血管疾病的危险因素，通过不确定的机制损伤内皮细胞。我们先前在培养的人血管内皮细胞中鉴定了几个同型半胱氨酸应答基因，包括内质网（ER）驻留分子伴侣GRP 78/BiP。在这里，我们证明，同型半胱氨酸诱导ER应激反应，并导致一种新的蛋白质，Herp，含有一个泛素样结构域的N端的表达。Herp的mRNA表达强烈上调诱导剂的ER应激，包括巯基乙醇，衣霉素，A23187，和毒胡萝卜素。在蛋白水平上也观察到ER应激依赖的Herp诱导。使用Herp特异性抗体的免疫化学分析表明Herp是一种54 kDa的膜相关ER蛋白。Herp是受ER应激反应途径调节的第一个完整膜蛋白。N端和C端都面向ER的胞质侧;这种膜拓扑结构使得Herp不太可能作为ER中蛋白质的分子伴侣，与GRP 78和其他ER应激反应蛋白相反。因此，疱疹病毒可能在细胞对压力的生存反应中起着未知的作用。
Hyperhomocysteinemia, a risk factor for vascular disease, injures endothelial cells through undefined mechanisms. We previously identified several homocysteine-responsive genes in cultured human vascular endothelial cells, including the endoplasmic reticulum (ER)-resident molecular chaperone GRP78/BiP. Here, we demonstrate that homocysteine induces the ER stress response and leads to the expression of a novel protein, Herp, containing a ubiquitin-like domain at the N terminus. mRNA expression of Herp was strongly upregulated by inducers of ER stress, including mercaptoethanol, tunicamycin, A23187, and thapsigargin. The ER stress-dependent induction of Herp was also observed at the protein level. Immunochemical analyses using Herp-specific antibodies indicated that Herp is a 54-kDa, membrane-associated ER protein. Herp is the first integral membrane protein regulated by the ER stress response pathway. Both the N and C termini face the cytoplasmic side of the ER; this membrane topology makes it unlikely that Herp acts as a molecular chaperone for proteins in the ER, in contrast to GRP78 and other ER stress-responsive proteins. Herp may, therefore, play an unknown role in the cellular survival response to stress.