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Regulating amyloid precursor protein synthesis through an internal ribosomal entry site
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. Littl...
Autores principales: | , , |
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Formato: | Texto |
Lenguaje: | English |
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Oxford University Press
2008
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2588504/ https://www.ncbi.nlm.nih.gov/pubmed/18953033 http://dx.doi.org/10.1093/nar/gkn792 |
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author | Beaudoin, Monique E. Poirel, Vincent-Joseph Krushel, Leslie A. |
author_facet | Beaudoin, Monique E. Poirel, Vincent-Joseph Krushel, Leslie A. |
author_sort | Beaudoin, Monique E. |
collection | PubMed |
description | 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. |
format | Text |
id | pubmed-2588504 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2008 |
publisher | Oxford University Press |
record_format | MEDLINE/PubMed |
spelling | pubmed-25885042009-03-04 Regulating amyloid precursor protein synthesis through an internal ribosomal entry site Beaudoin, Monique E. Poirel, Vincent-Joseph Krushel, Leslie A. Nucleic Acids Res Molecular Biology 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. Oxford University Press 2008-12 2008-10-25 /pmc/articles/PMC2588504/ /pubmed/18953033 http://dx.doi.org/10.1093/nar/gkn792 Text en © 2008 The Author(s) http://creativecommons.org/licenses/by-nc/2.0/uk/ This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/2.0/uk/) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited. |
spellingShingle | Molecular Biology Beaudoin, Monique E. Poirel, Vincent-Joseph Krushel, Leslie A. Regulating amyloid precursor protein synthesis through an internal ribosomal entry site |
title | Regulating amyloid precursor protein synthesis through an internal ribosomal entry site |
title_full | Regulating amyloid precursor protein synthesis through an internal ribosomal entry site |
title_fullStr | Regulating amyloid precursor protein synthesis through an internal ribosomal entry site |
title_full_unstemmed | Regulating amyloid precursor protein synthesis through an internal ribosomal entry site |
title_short | Regulating amyloid precursor protein synthesis through an internal ribosomal entry site |
title_sort | regulating amyloid precursor protein synthesis through an internal ribosomal entry site |
topic | Molecular Biology |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2588504/ https://www.ncbi.nlm.nih.gov/pubmed/18953033 http://dx.doi.org/10.1093/nar/gkn792 |
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