Skip Navigation


Nucleic Acids Research Advance Access originally published online on October 25, 2008
Nucleic Acids Research 2008 36(21):6835-6847; doi:10.1093/nar/gkn792
This Article
Right arrow Full Text Freely available
Right arrow Print PDF (1944K) Freely available
Right arrow Screen PDF (512K) Freely available
Right arrow Supplementary Data
Right arrowOA All Versions of this Article:
36/21/6835    most recent
gkn792v1
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in ISI Web of Science
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Add to My Personal Archive
Right arrow Download to citation manager
Right arrow Search for citing articles in:
ISI Web of Science (1)
Right arrow Commercial Re-use Guidelines
for Open Access NAR Content
Google Scholar
Right arrow Articles by Beaudoin, M. E.
Right arrow Articles by Krushel, L. A.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Beaudoin, M. E.
Right arrow Articles by Krushel, L. A.
Social Bookmarking
Add to CiteULike   Add to Connotea   Add to Del.icio.us  
What's this?

Nucleic Acids Research, 2008, Vol. 36, No. 21 6835-6847
© 2008 The Author(s)
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.

Molecular Biology

Regulating amyloid precursor protein synthesis through an internal ribosomal entry site

Monique E. Beaudoin1,2, Vincent-Joseph Poirel3 and Leslie A. Krushel1,2,3,*

1Neurosciences Program, 2Department of Biochemistry and Molecular Genetics and 3Department of Pharmacology, University of Colorado Denver School of Medicine, Aurora, CO 80045, USA

*To whom correspondence should be addressed. Tel: +303 724 3646; Fax: +303 724 3221; Email: leslie.krushel{at}uchsc.edu

Received June 3, 2008. Revised September 14, 2008. Accepted October 10, 2008.

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.

Present address: Vincent-Joseph Poirel, Institut des Neurosciences Cellulaires et Integratives, CNRS-UMR 7168, Strasbourg, France


Add to CiteULike CiteULike   Add to Connotea Connotea   Add to Del.icio.us Del.icio.us    What's this?




Disclaimer: Please note that abstracts for content published before 1996 were created through digital scanning and may therefore not exactly replicate the text of the original print issues. All efforts have been made to ensure accuracy, but the Publisher will not be held responsible for any remaining inaccuracies. If you require any further clarification, please contact our Customer Services Department.