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首页> 外文期刊>Proceedings of the National Academy of Sciences of the United States of America >Regulation of inducible nitric oxide synthase by aggresome formation
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Regulation of inducible nitric oxide synthase by aggresome formation

机译:聚集体形成对诱导型一氧化氮合酶的调控

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摘要

Misfolding and aggregation of proteins play an important part in the pathogenesis of several genetic and degenerative diseases. Recent evidence suggests that cells have evolved a pathway that involves sequestration of aggregated proteins into specialized "holding stations" called aggresomes. Here we show that cells regulate inducible NO synthase (iNOS), an important host defense protein, through aggresome formation. iNOS aggresome formation depends on a functional dynein motor and the integrity of the microtubules. The iNOS aggresome represents a "physiologic aggresome" and thus defines a new paradigm for cellular regulation of protein processing. This study indicates that aggresome formation in response to misfolded proteins may merely represent an acceleration of an established physiologic regulatory process for specific proteins whose regulation by aggresome formation is deemed necessary by the cell.
机译:蛋白质的错误折叠和聚集在几种遗传和退化性疾病的发病机理中起着重要的作用。最近的证据表明,细胞已经进化出一条途径,其中涉及将聚集的蛋白质螯合到专门的“聚集站”(称为聚集体)中。在这里,我们显示细胞通过聚集体形成调节可诱导的NO合酶(iNOS),一种重要的宿主防御蛋白。 iNOS聚集体的形成取决于功能性动力蛋白和微管的完整性。 iNOS集合体代表“生理性集合体”,因此定义了蛋白质加工的细胞调节的新范例。这项研究表明,响应于错误折叠的蛋白质而形成的聚集体仅代表特定蛋白质的已建立的生理调节过程的加速,这些特定蛋白质通过聚集体形成的调节被细胞认为是必需的。

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