Regulation of inducible nitric oxide synthase by aggresome formation
Regulation of inducible nitric oxide synthase by aggresome formation
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DOI：
10.1073/pnas.0500485102
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发表时间：
2005-03-29
影响因子：
11.1
通讯作者：
Eissa, NT
中科院分区：
文献类型：
--
作者：
Kolodziejska, KE;Burns, AR;Eissa, NT
蛋白质的错误折叠和聚集在多种遗传性疾病和退行性疾病的发病机制中发挥着重要作用。最近的证据表明，细胞已经进化出一种途径，涉及将聚集的蛋白质隔离到称为聚集体的专门“保持站”中。在这里，我们证明细胞通过聚集体形成来调节诱导型一氧化氮合酶（iNOS）（一种重要的宿主防御蛋白）。 NOS 聚集体的形成取决于功能性动力蛋白马达和微管的完整性。 NOS 攻击体代表“生理攻击体”，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，针对错误折叠蛋白质的聚集体形成可能仅仅代表了特定蛋白质的既定生理调节过程的加速，细胞认为这些蛋白质通过聚集体形成的调节是必要的。
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. NOS aggresome formation depends on a functional dynein motor and the integrity of the microtubules. The NOS 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.