Journal
GENE
Volume 488, Issue 1-2, Pages 1-12Publisher
ELSEVIER SCIENCE BV
DOI: 10.1016/j.gene.2011.06.004
Keywords
Alzheimer's disease; Amyloid beta; DNA-protein interaction; Gene regulation; Transcription factor
Categories
Funding
- Alzheimer's Association
- National Institutes of Health [AG18379, AG18884]
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Deposition of extracellular plaques, primarily consisting of amyloid beta peptide (A beta), in the brain is the confirmatory diagnostic of Alzheimer's disease (AD); however, the physiological and pathological role of A beta is not fully understood. Herein, we demonstrate novel A beta, activity as a putative transcription factor upon AD-associated genes. We used oligomers from 5'-flanking regions of the apolipoprotein E (APOE), A beta-precursor protein (APP) and beta-amyloid site cleaving enzyme-1 (BACE1) genes for electrophoretic mobility shift assay (EMSA) with different fragments of the A beta peptide. Our results suggest that A beta bound to an A beta-interacting domain (A beta ID) with a consensus of KGGRKTGGGG. This peptide-DNA interaction was sequence specific, and mutation of the first G of the decamer's terminal GGGG eliminated peptide-DNA interaction. Furthermore, the cytotoxic A beta 25-35 fragment had greatest DNA affinity. Such specificity of binding suggests that the A beta ID is worth of further investigation as a site wherein the A beta peptide may act as a transcription factor. (C) 2011 Elsevier B.V. All rights reserved.
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