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rdf:type |
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lifeskim:mentions |
umls-concept:C0002395,
umls-concept:C0002716,
umls-concept:C0017337,
umls-concept:C0054504,
umls-concept:C0150312,
umls-concept:C0179400,
umls-concept:C0332197,
umls-concept:C1364818,
umls-concept:C1366582,
umls-concept:C1704875,
umls-concept:C1705920,
umls-concept:C1710548
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pubmed:issue |
11
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pubmed:dateCreated |
2004-7-30
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pubmed:abstractText |
Potentially toxic amyloid beta-peptide (Abeta) in Alzheimer's disease (AD) is generated from a family of Abeta-containing precursor proteins (APP), which is regulated via the 5'-untranslated region (5'-UTR) of its mRNA. We analyzed 5'-UTRs of the APP superfamily, including amyloid plaque-forming and non-amyloid plaque-forming species, and of prions (27 different DNA sequences). A "CAGA" sequence proximal to the "ATG" start codon was present in a location unique to APP genes of amyloid plaque-forming species and absent in all other genes surveyed. This CAGA box is immediately upstream of an interleukin-1-responsive element (acute box). In addition, the proximal CAGA box is predicted to appear on a stem-loop structure in both human and guinea pig APP mRNA. This stem-loop is part of a predicted bulge-loop that encompasses a known iron regulatory element (IRE). Electrophoretic mobility shift with segments of the APP 5'-UTR showed that a region with the proximal CAGA sequence binds nuclear proteins, and this UTR fragment is active in a reporter gene functional assay. Thus, the 5'-UTR in the human APP but not those of APP-like proteins contains a specific region that may participate in APP regulation and may determine a more general model for amyloid generation as seen in AD. The 5'-UTR of human APP contains several interesting control elements, such as an acute box element, a CAGA box, an IRE, and a transforming growth factor-beta-responsive element, that could control APP expression and provide suitable and specific drug targets for AD.
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pubmed:grant |
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pubmed:language |
eng
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pubmed:journal |
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pubmed:citationSubset |
IM
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pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/5' Untranslated Regions,
http://linkedlifedata.com/resource/pubmed/chemical/Amyloid,
http://linkedlifedata.com/resource/pubmed/chemical/Amyloid beta-Protein Precursor,
http://linkedlifedata.com/resource/pubmed/chemical/Glutathione Peroxidase,
http://linkedlifedata.com/resource/pubmed/chemical/PRNP protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/Peptide Termination Factors,
http://linkedlifedata.com/resource/pubmed/chemical/Prions,
http://linkedlifedata.com/resource/pubmed/chemical/Prnp protein, mouse,
http://linkedlifedata.com/resource/pubmed/chemical/Protein Precursors,
http://linkedlifedata.com/resource/pubmed/chemical/RNA, Messenger,
http://linkedlifedata.com/resource/pubmed/chemical/SUP35 protein, S cerevisiae,
http://linkedlifedata.com/resource/pubmed/chemical/Saccharomyces cerevisiae Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/URE2 protein, S cerevisiae
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pubmed:status |
MEDLINE
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pubmed:month |
Aug
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pubmed:issn |
1530-6860
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pubmed:author |
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pubmed:issnType |
Electronic
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pubmed:volume |
18
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
1288-90
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pubmed:dateRevised |
2009-11-19
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pubmed:meshHeading |
pubmed-meshheading:15208260-5' Untranslated Regions,
pubmed-meshheading:15208260-Alzheimer Disease,
pubmed-meshheading:15208260-Amino Acid Sequence,
pubmed-meshheading:15208260-Amyloid,
pubmed-meshheading:15208260-Amyloid beta-Protein Precursor,
pubmed-meshheading:15208260-Animals,
pubmed-meshheading:15208260-Base Sequence,
pubmed-meshheading:15208260-Caenorhabditis elegans,
pubmed-meshheading:15208260-Cattle,
pubmed-meshheading:15208260-Cricetinae,
pubmed-meshheading:15208260-Drosophila melanogaster,
pubmed-meshheading:15208260-Fishes,
pubmed-meshheading:15208260-Gene Expression Regulation,
pubmed-meshheading:15208260-Genes, Reporter,
pubmed-meshheading:15208260-Glutathione Peroxidase,
pubmed-meshheading:15208260-Guinea Pigs,
pubmed-meshheading:15208260-Humans,
pubmed-meshheading:15208260-Mammals,
pubmed-meshheading:15208260-Mice,
pubmed-meshheading:15208260-Multigene Family,
pubmed-meshheading:15208260-Nucleic Acid Conformation,
pubmed-meshheading:15208260-PC12 Cells,
pubmed-meshheading:15208260-Peptide Termination Factors,
pubmed-meshheading:15208260-Prions,
pubmed-meshheading:15208260-Protein Folding,
pubmed-meshheading:15208260-Protein Precursors,
pubmed-meshheading:15208260-RNA, Messenger,
pubmed-meshheading:15208260-Rats,
pubmed-meshheading:15208260-Regulatory Sequences, Nucleic Acid,
pubmed-meshheading:15208260-Saccharomyces cerevisiae,
pubmed-meshheading:15208260-Saccharomyces cerevisiae Proteins,
pubmed-meshheading:15208260-Sequence Alignment,
pubmed-meshheading:15208260-Sequence Homology,
pubmed-meshheading:15208260-Species Specificity,
pubmed-meshheading:15208260-Structure-Activity Relationship,
pubmed-meshheading:15208260-Transfection
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pubmed:year |
2004
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pubmed:articleTitle |
Presence of a "CAGA box" in the APP gene unique to amyloid plaque-forming species and absent in all APLP-1/2 genes: implications in Alzheimer's disease.
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pubmed:affiliation |
Departments of Psychiatry, Institute of Psychiatric Research, Indiana University School of Medicine, Indianapolis, Indiana 46202, USA.
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pubmed:publicationType |
Journal Article,
Comparative Study,
Research Support, U.S. Gov't, P.H.S.,
Research Support, Non-U.S. Gov't
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