蛋白二硫键异构酶家族介导的癌症中的氧化还原调节。
Protein disulfide isomerase family mediated redox regulation in cancer.
机构信息
Department of Cell and Molecular Pharmacology and Experimental Therapeutics, Medical University of South Carolina, Charleston, SC, United States.
Department of Cell and Molecular Pharmacology and Experimental Therapeutics, Medical University of South Carolina, Charleston, SC, United States.
出版信息
Adv Cancer Res. 2023;160:83-106. doi: 10.1016/bs.acr.2023.06.001. Epub 2023 Jul 18.
Abstract
Protein disulfide isomerase (PDI) and its superfamilies are mainly endoplasmic reticulum (ER) resident proteins with essential roles in maintaining cellular homeostasis, via thiol oxidation/reduction cycles, chaperoning, and isomerization of client proteins. Since PDIs play an important role in ER homeostasis, their upregulation supports cell survival and they are found in a variety of cancer types. Despite the fact that the importance of PDI to tumorigenesis remains to be understood, it is emerging as a new therapeutic target in cancer. During the past decade, several PDI inhibitors has been developed and commercialized, but none has been approved for clinical use. In this review, we discuss the properties and redox regulation of PDIs within the ER and provide an overview of the last 5 years of advances regarding PDI inhibitors.
摘要
蛋白质二硫键异构酶（PDI）及其超家族主要是内质网（ER）驻留蛋白，通过巯基氧化/还原循环、伴侣蛋白和客户蛋白的异构化，在内质网稳态维持中发挥重要作用。由于 PDIs 在 ER 稳态中发挥重要作用，其上调支持细胞存活，并且存在于多种癌症类型中。尽管 PDIs 对肿瘤发生的重要性仍有待理解，但它正在成为癌症的一个新的治疗靶点。在过去的十年中，已经开发并商业化了几种 PDI 抑制剂，但没有一种被批准用于临床使用。在这篇综述中，我们讨论了 ER 中 PDIs 的特性和氧化还原调节，并概述了过去 5 年关于 PDI 抑制剂的进展。
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