When glycoproteins formed in the endoplasmic reticulum (ER) are misfolded, they are generally translocated into the cytosol for ubiquitination and are subsequently degraded by the proteasome. This system, the so-called ER-associated glycoprotein degradation, is important for eukaryotes to maintain the quality of glycoproteins generated in the ER. It has been established in yeast that several distinct proteins are involved in this translocation and degradation processes. Small glycopeptides formed in the ER are exported to the cytosol in a similar manner. This glycopeptide export system is conserved from yeast to mammalian cells, suggesting its basic biological significance for eukaryotic cells. These two export systems (for misfolded glycoproteins and glycopeptides) share some properties, such as a requirement for ATP and involvement of Sec61p, a central membrane protein presumably forming a dislocon channel for export of proteins. However, the machinery of glycopeptide export is poorly understood. In this study, various mutants known to have an effect on export/degradation of misfolded glycoproteins were examined for glycopeptide export activity with a newly established assay method. Surprisingly, most of the mutants were found not to exhibit a defect in glycopeptide export. The only gene that was found to be required on efficient export of both types of substrates was PMR1, the gene encoding the medial-Golgi Ca(2+)/Mn(2+)-ion pump. These results provide evidence that although the systems involved in export of misfolded glycoproteins and glycopeptides share some properties, they have exhibited distinct differences.

中文翻译：

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糖肽从内质网向细胞质的输出是由与错折叠糖蛋白的输出不同的机制介导的。

当在内质网（ER）中形成的糖蛋白错误折叠时，它们通常会转移到胞质溶胶中进行泛素化，随后被蛋白酶体降解。这个系统，即所谓的ER相关糖蛋白降解，对于真核生物维持ER中产生的糖蛋白的质量非常重要。在酵母中已经确定几种不同的蛋白质参与该转运和降解过程。ER中形成的小糖肽以类似方式输出到细胞质中。该糖肽输出系统从酵母到哺乳动物细胞都是保守的，表明其对真核细胞的基本生物学意义。这两个输出系统（针对错误折叠的糖蛋白和糖肽）具有某些特性，例如对ATP的要求和Sec61p的参与，中央膜蛋白大概形成了蛋白质输出的dislocon通道。但是，对糖肽输出的机制了解甚少。在这项研究中，使用新建立的测定方法检查了已知对错折叠糖蛋白的输出/降解有影响的各种突变体的糖肽输出活性。出乎意料的是，发现大多数突变体在糖肽输出中均未表现出缺陷。发现有效输出两种底物类型所需的唯一基因是PMR1，该基因编码内侧高尔基Ca（2 +）/ Mn（2+）离子泵。这些结果提供了证据，尽管涉及错误折叠的糖蛋白和糖肽输出的系统具有某些特性，但它们表现出明显的差异。