Sequestration of cellular interacting partners by protein aggregates: implication in a loss‐of‐function pathology
Sequestration of cellular interacting partners by protein aggregates: implication in a loss‐of‐function pathology
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DOI：
10.1111/febs.13722
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发表时间：
2016-10
期刊：
影响因子：
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通讯作者：
Hui Yang;Hong-Yu Hu
中科院分区：
文献类型：
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作者：
Hui Yang;Hong-Yu Hu
蛋白质错误折叠和聚集是几种神经退行性疾病（ND）的标志。然而，蛋白质聚集如何导致细胞毒性和神经变性仍然存在争议。新出现的证据表明，蛋白质聚集体对细胞相互作用伴侣的隔离有助于这些疾病的发病机制。本文就蛋白质聚集体对细胞蛋白质的螯合作用及其与蛋白质病的关系作一综述。基于不同的相互作用模式，我们将这些蛋白质螯合分为四种类型：蛋白质共聚集，结构域/基序介导的螯合，RNA辅助螯合和分子伴侣螯合。因此，被蛋白质聚集体劫持的细胞必需蛋白质和/或RNA可能失去其生物学功能，从而导致细胞毒性和神经变性。我们提出了一个劫持模型，概括了ND的隔离过程和功能丧失病理学。
Protein misfolding and aggregation are a hallmark of several neurodegenerative diseases (NDs). However, how protein aggregation leads to cytotoxicity and neurodegeneration is still controversial. Emerging evidence demonstrates that sequestration of cellular‐interacting partners by protein aggregates contributes to the pathogenesis of these diseases. Here, we review current research on sequestration of cellular proteins by protein aggregates and its relation to proteinopathies. Based on different interaction modes, we classify these protein sequestrations into four types: protein coaggregation, domain/motif‐mediated sequestration, RNA‐assisted sequestration, and sequestration of molecular chaperones. Thus, the cellular essential proteins and/or RNA hijacked by protein aggregates may lose their biological functions, consequently resulting in cytotoxicity and neurodegeneration. We have proposed a hijacking model recapitulating the sequestration process and the loss‐of‐function pathology of ND.