The Alzheimer's amyloid beta-peptide binds a specific DNA Abeta-interacting domain in the APP, BACE1, and APOE promoters in a sequence-specific manner: characterizing a new regulatory motif

Gene 488:1-12 (2011)
  Copy   BIBTEX

Abstract

Deposition of extracellular plaques, primarily consisting of amyloid beta peptide , in the brain is the confirmatory diagnostic of Alzheimer's disease ; however, the physiological and pathological role of Abeta is not fully understood. Herein, we demonstrate novel Abeta activity as a putative transcription factor upon AD-associated genes. We used oligomers from 5'-flanking regions of the apolipoprotein E , Abeta-precursor protein and beta-amyloid site cleaving enzyme-1 genes for electrophoretic mobility shift assay with different fragments of the Abeta peptide. Our results suggest that Abeta bound to an Abeta-interacting domain 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 Abeta25-35 fragment had greatest DNA affinity. Such specificity of binding suggests that the AbetaID is worth of further investigation as a site wherein the Abeta peptide may act as a transcription factor

Links

PhilArchive



    Upload a copy of this work     Papers currently archived: 94,593

External links

Setup an account with your affiliations in order to access resources via your University's proxy server

Through your library

Similar books and articles

Analytics

Added to PP
2015-06-29

Downloads
7 (#1,430,083)

6 months
1 (#1,749,371)

Historical graph of downloads
How can I increase my downloads?