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首页> 外文期刊>Cell Health and Cytoskeleton >EFP1 is an ER stress-induced glycoprotein which interacts with the pro-apoptotic protein Par-4
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EFP1 is an ER stress-induced glycoprotein which interacts with the pro-apoptotic protein Par-4

机译：EFP1是一种内质网应激诱导的糖蛋白，它与促凋亡蛋白Par-4相互作用

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Abstract: We have isolated the rat ortholog of EFP1 (EF-hand binding protein 1) as a novel interaction partner of the pro-apoptotic protein Par-4 (prostate apoptosis response-4). Rat EFP1 contains two thioredoxin domains, the COOH-terminal one harboring a CGFC motif, and has a similar protein domain structure as members of the protein disulfide isomerase (PDI) family. In REF52.2 and CHO cells, EFP1 colocalized with the endoplasmic reticulum (ER) marker PDI. Furthermore, EFP1 possesses catalytic activity as demonstrated by an insulin disulfide reduction assay. Western blot analysis revealed two EFP1 protein bands of approximately 136 and 155 kDa, representing different glycosylation states of the protein. Complex formation between EFP1 and Par-4 was confirmed in vitro and in vivo by co-immunoprecipitation, dot blot overlay and pull-down experiments. In CHO cells, coexpression of EFP1 and Par-4 resulted in enhanced Par-4-mediated apoptosis, which required the catalytic activity of EFP1. Interestingly, EFP1 was specifically upregulated in NIH3T3 cells after induction of ER stress by thapsigargin,?tunicamycin, and brefeldin A, but not by agents that induce oxidative stress or ER-independent apoptosis. Furthermore, we could show that the induction of apoptosis by Ca2+ stress-inducing agents was significantly decreased after siRNA oligonucleotide-mediated knockdown of Par-4. Our data suggest that EFP1 might represent a cell-protective enzyme that could play an important role in the decision between survival and initiation of Par-4-mediated apoptosis.
机译：摘要：我们已经分离出大鼠促排卵素EFP1（EF-手结合蛋白1）作为促凋亡蛋白Par-4（前列腺细胞凋亡反应-4）的新型相互作用伴侣。大鼠EFP1包含两个硫氧还蛋白域，其中一个COOH末端带有CGFC基序，并且具有与蛋白质二硫键异构酶（PDI）家族成员相似的蛋白质域结构。在REF52.2和CHO细胞中，EFP1与内质网（ER）标记PDI共定位。此外，EFP1具有催化活性，如胰岛素二硫化物还原试验所证实。蛋白质印迹分析显示两条EFP1蛋白条带，分别约为136和155 kDa，代表该蛋白的不同糖基化状态。通过共免疫沉淀，斑点印迹覆盖和下拉实验，在体外和体内证实了EFP1和Par-4之间的复合物形成。在CHO细胞中，EFP1和Par-4的共表达导致Par-4介导的细胞凋亡增强，这需要EFP1的催化活性。有趣的是，通过毒胡萝卜素，衣霉素和布雷菲德菌素A诱导ER应激后，NIH3T3细胞中EFP1特异性上调，但诱导氧化应激或不依赖ER的细胞凋亡的药物则没有。此外，我们可以证明，在siRNA寡核苷酸介导的Par-4敲低后，Ca2 +应激诱导剂诱导的细胞凋亡显着降低。我们的数据表明，EFP1可能代表一种细胞保护酶，该酶可能在Par-4介导的凋亡的存活与开始之间的决定中起重要作用。

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