UV Radiation Regulates Mi-2 through Protein Translation and Stability
UV Radiation Regulates Mi-2 through Protein Translation and Stability
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DOI：
10.1074/jbc.m805383200
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发表时间：
2008-12-12
影响因子：
4.8
通讯作者：
Archer, Trevor K.
中科院分区：
文献类型：
--
作者：
Burd, Craig J.;Kinyamu, H. Karimi;Archer, Trevor K.
皮肌炎（DM）是一种自身免疫性疾病，其通常伴随着针对SNF 2超家族解旋酶Mi-2的疾病特异性自身抗体的发展。最近的证据表明，紫外线辐射暴露可能是一个重要的危险因素，不仅发展的疾病，而且对Mi-2的特异性自身免疫。因此，我们研究了紫外线辐射对Mi-2蛋白表达的影响。我们观察到在细胞培养系统中暴露于紫外线辐射后蛋白质水平增加。这些表达的变化发生得相当迅速，在暴露后1小时最大化，并且与NuRD复合物的其他成员相比，Mi-2是独特的。蛋白质水平的变化不是通过转录机制介导的。处理导致通过转录物的5 '-UTR区域中的调节元件更有效地翻译信息。对蛋白质半衰期的研究进一步证明了UV暴露后Mi-2的稳定性增加。综上所述，我们描述了一种系统，通过该系统，Mi-2蛋白表达可以在UV暴露后迅速增加，然后维持长达16小时。这些数据提供了一种新的重要的转录调节因子的调节，并提供了深入了解DM和相关自身抗体的发展的可能机制。
Dermatomyositis (DM) is an autoimmune disease, which is often accompanied by the development of disease-specific autoantibodies directed against the SNF2-superfamily helicase, Mi-2. Recent evidence suggests that ultraviolet radiation exposure may be an important risk factor for the development of not only the disease but also specific autoimmunity against Mi-2. Consequently, we investigated the effects of ultraviolet radiation on Mi-2 protein expression. We observed an increase in protein levels upon ultraviolet radiation exposure in cell culture systems. These changes in expression occur quite rapidly, are maximized just 1 h following exposure, and are unique to Mi-2 when compared with other members of the NuRD complex. Changes in protein levels are not mediated through transcriptional mechanisms. Treatment results in a more efficiently translated message through regulatory elements in the 5'-UTR region of the transcript. Investigation into protein half-life further demonstrated increased stability of Mi-2 following UV exposure. Taken together, we describe a system by which Mi-2 protein expression can be quickly increased following UV exposure and then maintained up to 16 h later. These data provide a novel regulation of an important transcriptional regulator and provide insight into the possible mechanisms of the development of DM and associated autoantibodies.