Protein folding in the endoplasmic reticulum is an oxidative process that relies on protein disulfide isomerase (PDI) and endoplasmic reticulum oxidase 1 (ERO1). Over 30% of proteins require the chaperone PDI to promote disulfide bond formation. PDI oxidizes cysteines in nascent polypeptides to form disulfide bonds and can also reduce and isomerize disulfide bonds. ERO1 recycles reduced PDI family member PDIA1 using a FAD cofactor to transfer electrons to oxygen. ERO1 dysfunction critically affects several diseases states. Both ERO1 and PDIA1 are overexpressed in cancers and implicated in diabetes and neurodegenerative diseases. Cancer-associated ERO1 promotes cell migration and invasion. Furthermore, the ERO1-PDIA1 interaction is critical for epithelial-to-mesenchymal transition. Co-expression analysis of ERO1A gene expression in cancer patients demonstrated that ERO1A is significantly upregulated in lung adenocarcinoma (LUAD), glioblastoma and low-grade glioma (GBMLGG), pancreatic ductal adenocarcinoma (PAAD), and kidney renal papillary cell carcinoma (KIRP) cancers. ERO1Α knockdown gene signature correlates with knockdown of cancer signaling proteins including IGF1R, supporting the search for novel, selective ERO1 inhibitors for the treatment of cancer. In this review, we explore the functions of ERO1 and PDI to support inhibition of this interaction in cancer and other diseases.

中文翻译：

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ERO1-PDI相互作用在氧化蛋白折叠和疾病中的作用。

内质网中的蛋白质折叠是一种氧化过程，依赖于蛋白质二硫键异构酶（PDI）和内质网氧化酶1（ERO1）。超过30％的蛋白质需要伴侣PDI来促进二硫键的形成。PDI氧化新生多肽中的半胱氨酸以形成二硫键，并且还可以还原和异构化二硫键。ERO1使用FAD辅助因子将电子转移到氧气中，从而还原了还原的PDI家族成员PDIA1。ERO1功能障碍严重影响几种疾病状态。ERO1和PDIA1都在癌症中过表达，并与糖尿病和神经退行性疾病有关。癌症相关的ERO1促进细胞迁移和侵袭。此外，ERO1-PDIA1相互作用对于上皮到间质转化至关重要。癌症患者中ERO1A基因表达的共表达分析表明，ERO1A在肺腺癌（LUAD），胶质母细胞瘤和低度神经胶质瘤（GBMLGG），胰腺导管腺癌（PAAD）和肾肾乳头状细胞癌（KIRP）中明显上调。癌症。ERO1A基因敲低的基因标记与包括IGF1R在内的癌症信号蛋白的敲低相关，支持寻找新的选择性ERO1抑制剂来治疗癌症。在这篇综述中，我们探讨了ERO1和PDI的功能以支持抑制这种相互作用在癌症和其他疾病中的作用。ERO1A基因敲低的基因标记与包括IGF1R在内的癌症信号蛋白的敲低相关，支持寻找新的选择性ERO1抑制剂来治疗癌症。在这篇综述中，我们探讨了ERO1和PDI的功能以支持抑制这种相互作用在癌症和其他疾病中的作用。ERO1A基因敲低的基因标记与包括IGF1R在内的癌症信号蛋白的敲低相关，支持寻找新的选择性ERO1抑制剂来治疗癌症。在这篇综述中，我们探讨了ERO1和PDI的功能以支持抑制这种相互作用在癌症和其他疾病中的作用。