%0 Journal Article
%T A nuclear factor-binding domain in the 5'-untranslated region of the amyloid precursor protein promoter: Implications for the regulation of gene expression
%A Alexander A Vostrov
%A Michael J Taheny
%A Nerik Izkhakov
%A Wolfgang W Quitschke
%J BMC Research Notes
%D 2010
%I BioMed Central
%R 10.1186/1756-0500-3-4
%X The 5' untranslated region (UTR) of the APP gene, encompassing 147 base pairs between the transcriptional (+1) and the translational start site, was examined for its role in APP expression. Deletions close to the transcriptional start site reduced expression from the APP promoter in part by transcriptional mechanisms. However, deletions between position +50 and +104 had no effect on transcriptional activity while significantly reducing overall expression from the promoter. A nuclear factor-binding domain designated as DAPB was identified between position +72 and +115 of the 5'-APP-UTR. The binding-recognition sequence was localized between position +96 and +105. The same mutations that eliminated factor-binding also reduced expression from the APP promoter while having no effect on in vitro transcription or the RNA levels transcribed from transfected constructs.A nuclear factor-binding domain designated as DAPB was identified in the 5'-UTR of the APP gene. Elimination of factor-binding correlated with an overall decline in expression from the APP promoter while in vitro transcription and the total amount of in vivo transcribed RNA remained unaffected. This suggests that the binding-factor may have a function in post-transcriptional regulation, including nuclear export of mRNA.A neuropathological manifestation of Alzheimer disease and Down syndrome is the extracellular deposition of aggregated amyloid ¦Â-protein [1-3]. The Amyloid ¦Â-protein is derived from a group of larger differentially spliced proteins, the amyloid protein precursors (APP) [4]. There are three copies of the APP gene in Down syndrome and the level of APP transcript in the brains of afflicted individuals is increased about 4.5-fold [5]. A chimeric mouse model of Down syndrome shows increased APP transcription associated with cholinergic neuron degeneration [6]. Promoter mutations that increase the expression of APP are associated with the development of Alzheimer disease and a duplication of the APP
%U http://www.biomedcentral.com/1756-0500/3/4