Tissue-specific expression and dimerization of the endoplasmic reticulum oxidoreductase Ero1β
Tissue-specific expression and dimerization of the endoplasmic reticulum oxidoreductase Ero1β
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DOI：
10.1074/jbc.m505023200
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发表时间：
2005-09-23
影响因子：
4.8
通讯作者：
Benham, AM
中科院分区：
文献类型：
--
作者：
Dias-Gunasekara, S;Gubbens, J;Benham, AM
内质网氧化还原酶（Eros）是二硫键形成的关键酶。了解哺乳动物中的二硫键催化作用非常重要，因为蛋白质错误折叠涉及糖尿病，关节炎，癌症和衰老等疾病。哺乳动物表达两种相关的Ero蛋白，Ero 1 α和Ero 1 β。Ero 1 β的特征不完全，但具有生理学意义，因为它是由未折叠蛋白质反应诱导的。在这里，我们表明，Ero 1 β可以形成同源二聚体和混合异源二聚体与Ero 1 α，除了Ero-PDI二聚体。Ero-Ero二聚体需要Ero活性位点，在体内发生，并且可以建模到Ero 1 p晶体结构上。我们的数据表明，Ero 1 β蛋白在胃和胰腺中组成性强烈表达，但以细胞特异性方式表达。在胃中，Ero 1 β的选择性表达发生在产酶的主细胞中。在胰岛中，Ero 1 β表达较高，但与PDI和PDIp水平呈负相关，表明体内氧化蛋白折叠的调节存在细胞特异性差异。
Endoplasmic reticulum oxidoreductases (Eros) are essential for the formation of disulfide bonds. Understanding disulfide bond catalysis in mammals is important because of the involvement of protein misfolding in conditions such as diabetes, arthritis, cancer, and aging. Mammals express two related Ero proteins, Ero1 alpha and Ero1 beta. Ero1 beta is incompletely characterized but is of physiological interest because it is induced by the unfolded protein response. Here, we show that Ero1 beta can form homodimers and mixed heterodimers with Ero1 alpha, in addition to Ero-PDI dimers. Ero-Ero dimers require the Ero active site, occur in vivo, and can be modeled onto the Ero1p crystal structure. Our data indicate that the Ero1 beta protein is constitutively strongly expressed in the stomach and the pancreas, but in a cell-specific fashion. In the stomach, selective expression of Ero1 beta occurs in the enzyme-producing chief cells. In pancreatic islets, Ero1 beta expression is high, but is inversely correlated with PDI and PDIp levels, demonstrating that cell-specific differences exist in the regulation of oxidative protein folding in vivo.