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通过内部核糖体进入位点调控淀粉样前体蛋白的合成。

Regulating amyloid precursor protein synthesis through an internal ribosomal entry site.

作者信息

Beaudoin Monique E, Poirel Vincent-Joseph, Krushel Leslie A

机构信息

Department of Biochemistry, Neurosciences Program, University of Colorado Denver School of Medicine, Aurora, CO 80045, USA.

出版信息

Nucleic Acids Res. 2008 Dec;36(21):6835-47. doi: 10.1093/nar/gkn792. Epub 2008 Oct 25.

DOI:10.1093/nar/gkn792
PMID:18953033
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC2588504/
Abstract

Expression of amyloid precursor protein (APP) is critical to the etiology of Alzheimer's disease (AD). Consequently, regulating APP expression is one approach to block disease progression. To this end, APP can be targeted at the levels of transcription, translation, and protein stability. Little is currently known about the translation of APP mRNA. Here, we report that endogenous APP mRNA is translated in neural cell lines via an internal ribosome entry site (IRES) located in the 5'-untranslated leader. The functional unit of the APP IRES is located within the 5' 50 nucleotides of the 5'-leader. In addition, we found that the APP IRES is positively regulated by two conditions correlated with AD, increased intracellular iron concentration and ischemia. Interestingly, the enhancement of APP IRES activity is dependent upon de novo transcription. Taken together, our data suggest that internal initiation of translation of the APP mRNA is an important mode for synthesis of APP, a mechanism which is regulated by conditions that also contribute to AD.

摘要

淀粉样前体蛋白（APP）的表达对阿尔茨海默病（AD）的病因至关重要。因此，调节APP表达是阻止疾病进展的一种方法。为此，可以在转录、翻译和蛋白质稳定性水平上靶向APP。目前对APP mRNA的翻译了解甚少。在这里，我们报告内源性APP mRNA在神经细胞系中通过位于5'-非翻译前导区的内部核糖体进入位点（IRES）进行翻译。APP IRES的功能单元位于5'-前导区的5'端50个核苷酸内。此外，我们发现APP IRES受到与AD相关的两个条件的正向调节，即细胞内铁浓度升高和局部缺血。有趣的是，APP IRES活性的增强依赖于从头转录。综上所述，我们的数据表明APP mRNA的内部翻译起始是APP合成的一种重要模式，这一机制受同样导致AD的条件调节。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6e0f/2588504/964e13dc4983/gkn792f11.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6e0f/2588504/964e13dc4983/gkn792f11.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6e0f/2588504/148bb41b213f/gkn792f6.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6e0f/2588504/4ff4912cb788/gkn792f7.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6e0f/2588504/964e13dc4983/gkn792f11.jpg

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Neuroscience. 2008 Jun 23;154(2):504-20. doi: 10.1016/j.neuroscience.2008.03.057. Epub 2008 Apr 1.
3
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4
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7
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8
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9
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