Protein Disulfide Isomerase Superfamily in Disease and the Regulation of Apoptosis.
Protein Disulfide Isomerase Superfamily in Disease and the Regulation of Apoptosis.
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DOI：
10.2478/ersc-2013-0001
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发表时间：
2014-01
期刊：
影响因子：
--
通讯作者：
Townsend DM
中科院分区：
文献类型：
--
作者：
Grek C;Townsend DM
细胞内稳态需要大量信号级联的平衡，这些信号级联取决于必需蛋白质被正确合成、折叠并递送到适当的亚细胞位置。内质网（endoplasmic reticulum，ER）是真核细胞中一种特殊的细胞器，是分泌蛋白、膜蛋白和许多细胞器靶蛋白合成和折叠的中心。蛋白质折叠的完整性通过ATP、Ca++、分子伴侣以及氧化性氧化还原环境的存在而得以实现。蛋白质折叠的负荷和能力之间的不平衡导致称为ER应激的细胞状况。这些途径恢复ER稳态的失败导致凋亡途径的激活。蛋白质二硫键异构酶（PDI）是一类具有不同序列的氧化还原酶超家族，广泛分布于内质网、细胞核、细胞质、线粒体和细胞膜。PDI超家族具有多种功能，包括充当分子伴侣、蛋白质结合伴侣和激素储库。最近，PDI家族成员已被牵连在细胞凋亡信号转导事件的调节。定义从促生存到促死亡反应的转换的分子机制的复杂性被最近的研究所证明，这些研究揭示了特定的伴侣蛋白作为决定细胞命运的信号通路中的整合点的作用。以下综述讨论了在ER应激过程中PDI在细胞死亡和存活中的双重作用。
Cellular homeostasis requires the balance of a multitude of signaling cascades that are contingent upon the essential proteins being properly synthesized, folded and delivered to appropriate subcellular locations. In eukaryotic cells the endoplasmic reticulum (ER) is a specialized organelle that is the central site of synthesis and folding of secretory, membrane and a number of organelletargeted proteins. The integrity of protein folding is enabled by the presence of ATP, Ca++, molecular chaperones, as well as an oxidizing redox environment. The imbalance between the load and capacity of protein folding results in a cellular condition known as ER stress. Failure of these pathways to restore ER homeostasis results in the activation of apoptotic pathways. Protein disulfide isomerases (PDI) compose a superfamily of oxidoreductases that have diverse sequences and are localized in the ER, nucleus, cytosol, mitochondria and cell membrane. The PDI superfamily has multiple functions including, acting as molecular chaperones, protein-binding partners, and hormone reservoirs. Recently, PDI family members have been implicated in the regulation of apoptotic signaling events. The complexities underlying the molecular mechanisms that define the switch from pro-survival to pro-death response are evidenced by recent studies that reveal the roles of specific chaperone proteins as integration points in signaling pathways that determine cell fate. The following review discusses the dual role of PDI in cell death and survival during ER stress.
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