Protein localization in disease and therapy
Protein localization in disease and therapy
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DOI：
10.1242/jcs.089110
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发表时间：
2011-10-15
影响因子：
4
通讯作者：
Link, Wolfgang
中科院分区：
文献类型：
--
作者：
Hung, Mien-Chie;Link, Wolfgang
真核细胞被组织成覆盖着膜的隔间，这些隔间的特征是特定的蛋白质组和生化上不同的细胞过程。蛋白质适当的亚细胞定位是至关重要的，因为它为它们的功能提供了生理环境。在这篇评论中，我们简要概述了涉及蛋白质运输的不同机制，并描述了蛋白质的异常定位如何在许多人类疾病的发病机制中起作用，如代谢、心血管和神经退行性疾病，以及癌症。因此，修改与疾病相关的蛋白质亚细胞错位可能是一种有吸引力的治疗干预手段。特别是，将蛋白质折叠和细胞信号以及核输入和输出与蛋白质的亚细胞定位联系起来的细胞过程已被建议作为治疗干预的目标。我们讨论了治疗恢复被破坏的生理蛋白定位和治疗定位错误作为灭活致病蛋白的策略所涉及的概念。
The eukaryotic cell is organized into membrane-covered compartments that are characterized by specific sets of proteins and biochemically distinct cellular processes. The appropriate subcellular localization of proteins is crucial because it provides the physiological context for their function. In this Commentary, we give a brief overview of the different mechanisms that are involved in protein trafficking and describe how aberrant localization of proteins contributes to the pathogenesis of many human diseases, such as metabolic, cardiovascular and neurodegenerative diseases, as well as cancer. Accordingly, modifying the disease-related subcellular mislocalization of proteins might be an attractive means of therapeutic intervention. In particular, cellular processes that link protein folding and cell signaling, as well as nuclear import and export, to the subcellular localization of proteins have been proposed as targets for therapeutic intervention. We discuss the concepts involved in the therapeutic restoration of disrupted physiological protein localization and therapeutic mislocalization as a strategy to inactivate disease-causing proteins.